SlideShare uma empresa Scribd logo
1 de 32
Baixar para ler offline
“ IHC is an Important Complimentary Tool
for Diagnosis of Cancer”
Lawrence T. Richards
M.S.,H.T(ASCP), QIHC(ASCP)

Consultant,
Bio Marker Assay Development,
Santa Barbara, California.
For teaching purpose only
“ The Diagnostic Power of any
Immunohistochemical Procedure is
no Greater than the wisdom of the
Pathologist interpreting it.”
Dr.Allen M.Gown
IHC as a compliment to H&E
• Is H&E alone not enough?
• Is Special Stain not enough?
• Is IHC alone enough?
Special Stain

Antibody for Yeast

Budding yeast GMS Stain and H&E (Blastomycosis).

AFB

HP Alcian YellowToluidine Blue
Special stain vs IHC
H.pylori
Alcian Yellow-Toluidine Blue

H.Pylori antibody
Immunohistochemistry is an important complimentary tool for diagnosis of cancer"
Usefulness of IHC tests.
• Poorly differentiated tumors and mixed carcinomas
• Undifferentiated tumors of unknown origin
• Treatment based on sub-type of cancer: Personalized
Medicine eg., Breast Ca
• Monitoring progress of cancer (Predictive and Prognosis)
• In Malignant Lymphoma,
• In identifying Carcinoid (Neuroendocrine) tumors
• In Cytologic specimens
IHC helps in deciding Treatments
ER/PR

About 75% of all breast cancers are “ER positive.” They grow in response to the
hormone estrogen. About 65% of these are also “PR positive.” They grow in response
to another hormone, progesterone.
If your breast cancer’s cells have a significant number of receptors for either estrogen
or progesterone, your cancer is considered hormone-receptor positive and likely to
respond to endocrine therapies
Breast cancer tumors that are ER/PR-positive are 60% likely to respond to endocrine
therapy. Tumors that are ER/PR negative are only 5% to 10% likely to respond to
endocrine therapy
Her2
In about 20% to 25% of breast cancers, the cancer cells make too much of a protein
known as HER2/neu. These breast cancers tend to be much more aggressive and
fast-growing.
For women with HER2-positive breast cancers, the drug Herceptin has been shown to
dramatically reduce the risk of recurrence
Triple Negative
Some breast cancers -- estimates range between 10% and 17% -- are known as “triple
negative” because they lack estrogen and progesterone receptors and do not
overexpress the HER2 protein. The majority of breast cancers associated with the
breast cancer gene known as BRCA1 are triple negative.
These cancers generally respond well to adjuvant chemotherapy
http://www.webmd.com/breast-cancer/breast-cancer-types-er-positive-her2-positive
Immunohistochemistry is an important complimentary tool for diagnosis of cancer"
Histiogenic Dx of Neoplasm
• ID of proliferation of cells

Epithelium

NeuroEndocrine

Melanocyte

A) Expression of cytokeratin AE1/AE3 in lung carcinosarcoma ; B) chromogranin
expression in gastric neuroendocrine carcinoma ; C) HMB 45 immunostainning in
melanoma .
Immunohistochemistry is an important complimentary tool for diagnosis of cancer"
Metastatic Adenocarcinoma of
unknown origin
with site specific markers

PSA

(-) +
TTF-1
(-) +
GCDFP15 +
(-)
CDX2 / CK20

Colon
Lung
CDX2
CK 7

Mesothelin

(-) +
(-) +
Mesothelin
(-) +
Lysozyme
+
(-)
CA125

+
(-)

(-) +
ER

MC5+ (98%)

Prostate

+

Breast

Stomach/Pancreas

+

(-)
Ovary

(-)

Breast
Pancreas,(Ovary serous)
Stomach / Pancreas
Stomach / Pancreas

Breast / Stomach / Pancreas
Source: www.clincancerres.aacrjournals.org/egi/content/full/11/10/3766

Colon
Endocervical Ad.Ca &
Endometrial Mucinous Ad.Ca
ECA
•
•
•
•

MUC-1(-)
ER(-)
PR(-)
P16(+)

EMMA
•
•
•
•

MUC-1 (+)
ER(+)
PR(+)
P16(-)

Khoury T et al.BMC Clin Path 2006;6:1
Prostate Ca or Benign ?
• Prostate
Cancer
•
•
•
•
•
•
•
•

EpCam +
ATM +
AMACR +
PSA + / (-)
34ßE12 (-) almost all
p63 (-) almost all
Prostein +
NKX3.1 +

• Benign Prostate
•
•
•
•
•
•
•
•

EpCam (-)
ATM (-) / +
AMACR (-)
PSA + / (-)
34ßE12 +
p63 +
Prostein +
NKX3.1 +

ATM=ataxia-telangiectasia mutated;AMACR=alpha-methylacyl-CoA racemase;Ep-Cam=epithelial transmembrane glycoprotein
Hammerich KH et al.Application of Immunohistochemistry to the Genitourinary System(Prostate, Urinary
Bladder, Testis, and Kidney)Archives of Pathology and Laboratory Medicine;132:432-440,2007
Urothelial Ca vs Prostate Ca
Urothelial ca

•
•
•
•
•
•
•
•
•
•

EMA
CK7
P63
CK5/6
EpCam
CD57
PSA
PAP
NKX3.1
Prostei
n

Prostate ca

+
+
+/0
+/0
+/0
-/+ +/0
+
0
+/0
+
0
+
0
+

Hammerich KH.Archives of Pathology and Laboratory Medicine;132(3):432-440

Urothelial ca

Prostate ca
Prognastic
Risk Biomarkers (or screening
biomarkers) Describe risk of cancer
occurrence or cancer progression because they
are implicated in neoplastic progression and
include:
1. Genetic predisposition (e.g., BRCA1/2)
2. Over expression of genes (e.g., BCRABLTyrosin Kinase Inhibitor in CML, HER-2/neu in Br Ca,PTEN,
RAS,Colo Rectal Cancer AKTin Pancreatic cancer)
4.Environmental factors and lifestyle (e.g., HPV or
HBV infection
http://www.esmo.org/content/download/8713/176680/file/
The-use-of-Biomarkers-for-Treatment-Sessa-Fasolo.pdf
Undifferentiated Tumors
Use of IHC to differentiate broad lineage

Pan CK
AE1/AE3

CD45
(LCA)

HMB45
or S100

VIM

Carcinoma

Positive

Negative Negative Negative

Melanoma

Negative

Negative Positive

Sarcoma

Negative

Negative Negative Positive

Lymphoma

Negative

Positive

Positive

Negative Negative
Carcinoma
Use of CK7 and CK20
CK7 +
CK20 +

CK7 +
CK20 -

CK7 –
CK20 +

CK7 –
CK20 -

Urothelial Ca
Pancreatic Ad Ca
OvarianMucinous
Ca
Ad Ca of Bladder
Gastric Ad Ca
Cholangio Ca
subset

Breast Ca
EndoMetrial Ad Ca
EndoCervical Ad Ca
Ovarian Cerous Ca
Lung Ad Ca
Cholangio Ca
LungSmCC
Mesothelioma
Thyroid Ca
SCC of Cervix
SalivaryGland
tumors
Urothelial Ca subset
Pancreatic and
Gastric Ad Ca
subset

Colorectal Ad Ca
Markel Cell ca
Gastric Ad Ca
subset

Prostate Ad Ca
SCC
RCC
HCC
Mesothelioma
AdrenoCortical ca
NonSeminoma
LungSmCC
minorSubset
Gastric Ad Ca
subset

http://www.pathinformatics.com/department/documents/SusanE%20Lecture.pdf
Immunohistochemistry stains in
squamous cell carcinoma and
adenocarcinoma of lung. H&E:
hematoxylin and eosin; CK:
cytokeratin; TTF-1: thyroid
transcription factor 1. Squamous
carcinomas are typically positive
for CK5/6 and P63, and
negative for CK7 and TTF-1,
with the reverse profile for
adenocarcinoma although this
case of squamous cell
carcinoma demonstrates focal
weak staining for CK7.

SqCC

AdCa

“Ancillary Testing in Lung Cancer Diagnosis”
Dublinski et al.
Openi.nlm.nih.gov
Primary and Additional Markers

For teaching purpose only
For teaching purpose only
CK7 and CK20

For teaching purpose only
http://www.pathinformatics.com/department/documents/SusanE%20Lecture.pdf
Metastatic AdenoCarcinoma from Unknown Primary

Tumors from Unknown Primary Site

http://www.translational-medicine.com/content/pdf/1479-5876-10-12.pdf

For teaching purpose only
CUP Diagnosis
(Cancer of Unknown Primary)
For teaching purpose only

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631214/figure/f1-gcr1_6p0229/
Prostate Ca vs Urothelial Ca
Cancer PSA/ CKPSAP hmw

CK7 CK20

Prostate
+
Adenoca few -

few +

foc +

foc +

Urothelial Ca

+
few -

+
rare -

+/-

CK17 T -Mod CEAm CD57
Leu 7

6%+

-

foc +

+
few -

+/-

+
60-90% foc +

http://www.ihcworld.com/_newsletter/2001/focus_mar_2001.pdf

+
few-
Immunoperoxidase Panel for Liver Lesions
Hepatocellular

Colon

Biliary

Pancreas

Ovary
/EM

Sarcoma

Hepar

+

-

-

-

-

-

AFP

+

-

-

-

-

-

CEA

-

+

+

+/-

+/-

-

CK7

-

-

+

+

+

-

CK20

-

+

?

?

-

-

AE1
AE3

+/-

+

+/-

+

+

-

CA 19-9

-

-

-

+

-

-

ER

+
(Not for Renal Cell Carcinoma).
(?) suggests could be positive 35% to 65% or negative);
and +/- dependent on subtype of histology from that organ.

-
Napsin A + TTF-1
Napsin A, an aspartic acid protease whose
expression in the lung is regulated by
TTF-1, has also shown promise in helping
to differentiate primary lung from
metastatic adenocarcinomas. While
Napsin A expression may also be seen in
normal kidney and in a proportion of renal
tumors, positivity for both TTF-1 and
napsin A is a strong indication that an
adenocarcinoma originated from lung .
Examples of common panels of Antibodies Used
Generic T-cell Vs B-Cell : CD3, CD20, CD45
Folicular Lymphoma Vs Hyperplasia: Bcl2, Bcl6, CD3, CD10,CD20
Low Grade B Lymphoma: CD3, CD5, CD10, CD20, CD23,
CD43, Bcl2, Bcl6,

MALT Lymphoma: CD3, Cd5, CD20, Bcl2, ISH Kappa and Lambda
Hodgkin’s Lymphoma: CD3, CD15, CD20, CD30, CD45
Myeloma: CD138, ISH Kappa and Lambda
Carcinoma Vs Lymphoma: CD3, CD20, CD45, PanCK
Metastatic Carcinoma: CK7, CK20, TTF-1
GIST: CD117, CD34, S100, Desmin, SMA
Mesothelioma: PanCK, CK5/6, Calret, TTF-1, CEA, CD15
If male add PSA/ if female add BRST2
Antibodies commonly used
•

Breast
ER, PR, gross cystic fluid protein, CK7,CK20, E-cadherin

•

Colon and other GI tract
CEA (monoclonal), CK7, CK20

•

Germ cell

PLAP, -fetoprotein, -HCG, AE1/3
• Hepatocellular
Hepar, -fetoprotein, CK7, CK20, AE1 and AE3 (separately)
• Lung
TTF-1, CK7, CK20, CEA, Ber-EP4, chromogranin, synaptophysin, S100
• Lymphoma
LCA (CD45RB monoclonal), CD3, CD20, CD30, ALK-1,
myeloperoxidase, and light chains, Bcl-2
Antibodies commonly used contd.

• Mesothelioma: Calretinin, AE1, AE3
• Melanoma: S100 (when spindled cells), HMB-45
•
•
•
•
•
•
•

(when epithelioid), MART1
Neuroendocrine : Chromogranin, synaptophysin, NSE
Pancreas : AE1/3, CK7, CK20, CA 19-9, CEA, chromogranin,
synaptophysin, -antichymotrypsin, CD10, PR, Ber-EP4
Prostate :PSA, CK7, CK20
Renal: EMA, CD10, HMB-45,
inhibin- (to exclude adrenal /cortical)
Sarcoma : Vimentin, S100, CD117 (c-Kit), CD34,SMA, myogenin,
CD31, CD68, desmin,CD1a, CD99
Thyroid: TTF-1, thyroglobulin, calcitonin, CEA
Urothelial : CK7, CK20,Uroplakin
Conclusion
Thank you for giving me an opportunity to
share my knowledge with you all.
It is my hope that that this presentation will
fulfill the goal of providing the attendees a
little insight into the powerful tool of IHC in
diagnosis of difficult cases and help in
monitoring disease progression in patients
and course correction in treatment
procedures.
Acknowledgements
New York University
-Department of Environmental Medicine
DAKO
-Research and Development
Quest Diagnostics
-Clinical Trials and Bio-Marker

Development
Immunohistochemistry is an important complimentary tool for diagnosis of cancer"

Mais conteúdo relacionado

Mais procurados

Gastrointestinal Tumour Markers
Gastrointestinal Tumour MarkersGastrointestinal Tumour Markers
Gastrointestinal Tumour MarkersRatnadeep Ganguly
 
Reporting thyroid fine needle aspiration by the bethesda system
Reporting thyroid fine needle aspiration by the bethesda systemReporting thyroid fine needle aspiration by the bethesda system
Reporting thyroid fine needle aspiration by the bethesda systemMonika Nema
 
病理-IHC免疫組織染色
病理-IHC免疫組織染色病理-IHC免疫組織染色
病理-IHC免疫組織染色Gem Wu
 
Recent andvances hodgkins lymphoma
Recent andvances  hodgkins lymphomaRecent andvances  hodgkins lymphoma
Recent andvances hodgkins lymphomaSumanth Deva
 
Focal and diffuse lesions of liver
Focal and diffuse lesions of liverFocal and diffuse lesions of liver
Focal and diffuse lesions of liverAGRAWAL14
 
FIGO staging of endometrial cancer 2023.ppt
FIGO staging of endometrial cancer 2023.pptFIGO staging of endometrial cancer 2023.ppt
FIGO staging of endometrial cancer 2023.pptDr Seena Tresa Samuel
 
HEPATOCELLULAR CARCINOMA RADIOLOGY
HEPATOCELLULAR CARCINOMA RADIOLOGYHEPATOCELLULAR CARCINOMA RADIOLOGY
HEPATOCELLULAR CARCINOMA RADIOLOGYRMLIMS
 
The Paris System for Reporting Urinary Cytology
The Paris System for Reporting Urinary CytologyThe Paris System for Reporting Urinary Cytology
The Paris System for Reporting Urinary CytologyRawa Muhsin
 
Immunohistochemistry in lung cancer
Immunohistochemistry in lung cancerImmunohistochemistry in lung cancer
Immunohistochemistry in lung cancerRikin Hasnani
 
CT and MRI Imaging of Hepatic metastases
CT and MRI Imaging of Hepatic metastasesCT and MRI Imaging of Hepatic metastases
CT and MRI Imaging of Hepatic metastasesDr Priyanka Vishwakarma
 
Pathology of Endometrial cancer 2022.pptx
Pathology of Endometrial cancer 2022.pptxPathology of Endometrial cancer 2022.pptx
Pathology of Endometrial cancer 2022.pptxDr ABU SURAIH SAKHRI
 
Molecular Genetics and Recent updates of Soft tissue tumours Dr.Argha Baruah
Molecular Genetics and Recent updates of Soft tissue tumours Dr.Argha BaruahMolecular Genetics and Recent updates of Soft tissue tumours Dr.Argha Baruah
Molecular Genetics and Recent updates of Soft tissue tumours Dr.Argha BaruahArgha Baruah
 
Diagnostic approach to metastatic adenocarcinoma
Diagnostic approach to metastatic adenocarcinomaDiagnostic approach to metastatic adenocarcinoma
Diagnostic approach to metastatic adenocarcinomaSivaranjini N
 

Mais procurados (20)

Ca endometrium
Ca endometriumCa endometrium
Ca endometrium
 
Gastrointestinal Tumour Markers
Gastrointestinal Tumour MarkersGastrointestinal Tumour Markers
Gastrointestinal Tumour Markers
 
Reporting thyroid fine needle aspiration by the bethesda system
Reporting thyroid fine needle aspiration by the bethesda systemReporting thyroid fine needle aspiration by the bethesda system
Reporting thyroid fine needle aspiration by the bethesda system
 
病理-IHC免疫組織染色
病理-IHC免疫組織染色病理-IHC免疫組織染色
病理-IHC免疫組織染色
 
Recent andvances hodgkins lymphoma
Recent andvances  hodgkins lymphomaRecent andvances  hodgkins lymphoma
Recent andvances hodgkins lymphoma
 
Neuroblastoma
Neuroblastoma Neuroblastoma
Neuroblastoma
 
MANAGEMENT OF LUMINAL BREAST CANCER.pptx
MANAGEMENT OF LUMINAL BREAST CANCER.pptxMANAGEMENT OF LUMINAL BREAST CANCER.pptx
MANAGEMENT OF LUMINAL BREAST CANCER.pptx
 
Focal and diffuse lesions of liver
Focal and diffuse lesions of liverFocal and diffuse lesions of liver
Focal and diffuse lesions of liver
 
FIGO staging of endometrial cancer 2023.ppt
FIGO staging of endometrial cancer 2023.pptFIGO staging of endometrial cancer 2023.ppt
FIGO staging of endometrial cancer 2023.ppt
 
HEPATOCELLULAR CARCINOMA RADIOLOGY
HEPATOCELLULAR CARCINOMA RADIOLOGYHEPATOCELLULAR CARCINOMA RADIOLOGY
HEPATOCELLULAR CARCINOMA RADIOLOGY
 
ROMA (Risk of Ovarian Malignancy Algorithm)
ROMA (Risk of Ovarian Malignancy Algorithm)ROMA (Risk of Ovarian Malignancy Algorithm)
ROMA (Risk of Ovarian Malignancy Algorithm)
 
The Paris System for Reporting Urinary Cytology
The Paris System for Reporting Urinary CytologyThe Paris System for Reporting Urinary Cytology
The Paris System for Reporting Urinary Cytology
 
Immunohistochemistry in lung cancer
Immunohistochemistry in lung cancerImmunohistochemistry in lung cancer
Immunohistochemistry in lung cancer
 
Liver cytology
Liver cytologyLiver cytology
Liver cytology
 
Malignant renal-masses-in-pediatrics
Malignant renal-masses-in-pediatricsMalignant renal-masses-in-pediatrics
Malignant renal-masses-in-pediatrics
 
CT and MRI Imaging of Hepatic metastases
CT and MRI Imaging of Hepatic metastasesCT and MRI Imaging of Hepatic metastases
CT and MRI Imaging of Hepatic metastases
 
Pathology of Endometrial cancer 2022.pptx
Pathology of Endometrial cancer 2022.pptxPathology of Endometrial cancer 2022.pptx
Pathology of Endometrial cancer 2022.pptx
 
Molecular Genetics and Recent updates of Soft tissue tumours Dr.Argha Baruah
Molecular Genetics and Recent updates of Soft tissue tumours Dr.Argha BaruahMolecular Genetics and Recent updates of Soft tissue tumours Dr.Argha Baruah
Molecular Genetics and Recent updates of Soft tissue tumours Dr.Argha Baruah
 
Diagnostic approach to metastatic adenocarcinoma
Diagnostic approach to metastatic adenocarcinomaDiagnostic approach to metastatic adenocarcinoma
Diagnostic approach to metastatic adenocarcinoma
 
Update on soft tissue tumors
Update on soft tissue tumors Update on soft tissue tumors
Update on soft tissue tumors
 

Semelhante a Immunohistochemistry is an important complimentary tool for diagnosis of cancer"

Cancer and ihc markers
Cancer and ihc markersCancer and ihc markers
Cancer and ihc markersNilesh Kucha
 
Management of ca unknown primary
Management of ca unknown primaryManagement of ca unknown primary
Management of ca unknown primaryVarshu Goel
 
Tumour markers with Recent Advances
Tumour markers with Recent AdvancesTumour markers with Recent Advances
Tumour markers with Recent AdvancesPrince Lokwani
 
Case 3
Case 3Case 3
Case 3kciapm
 
Use of Autoantibodies to detect the onset of breast cancer
Use of Autoantibodies to detect the onset of breast cancerUse of Autoantibodies to detect the onset of breast cancer
Use of Autoantibodies to detect the onset of breast cancerIsabelle Chiu
 
Using biomarkers to monitor the dynamics of tumor
Using biomarkers to monitor the dynamics of tumorUsing biomarkers to monitor the dynamics of tumor
Using biomarkers to monitor the dynamics of tumorsummer elmorshidy
 
Ovariancancer
OvariancancerOvariancancer
Ovariancancerraj kumar
 
TUMOR MARKERS OF COLORECTAL CARCINOMA
TUMOR MARKERS OF  COLORECTAL CARCINOMATUMOR MARKERS OF  COLORECTAL CARCINOMA
TUMOR MARKERS OF COLORECTAL CARCINOMAMoustafa Rezk
 
Gynecologic Tumor Markers
Gynecologic  Tumor  MarkersGynecologic  Tumor  Markers
Gynecologic Tumor Markerswaleed shehadat
 
Diagnostic tools in oncology
Diagnostic tools in oncologyDiagnostic tools in oncology
Diagnostic tools in oncologyMohammed Fathy
 
12- Tumor marker .pdf
12- Tumor marker .pdf12- Tumor marker .pdf
12- Tumor marker .pdfa51hi2in
 
TESTICULAR TUMORS Etiopathogenesis, Features and Treatment
TESTICULAR TUMORS Etiopathogenesis, Features and TreatmentTESTICULAR TUMORS Etiopathogenesis, Features and Treatment
TESTICULAR TUMORS Etiopathogenesis, Features and TreatmentSomanath Sharma
 

Semelhante a Immunohistochemistry is an important complimentary tool for diagnosis of cancer" (20)

Cancer Dx Algorithm
Cancer Dx AlgorithmCancer Dx Algorithm
Cancer Dx Algorithm
 
Cancer and ihc markers
Cancer and ihc markersCancer and ihc markers
Cancer and ihc markers
 
Tumour marker
Tumour markerTumour marker
Tumour marker
 
Breast Cancer
Breast CancerBreast Cancer
Breast Cancer
 
Management of ca unknown primary
Management of ca unknown primaryManagement of ca unknown primary
Management of ca unknown primary
 
Use of algorithm in IHC
Use of algorithm in IHCUse of algorithm in IHC
Use of algorithm in IHC
 
Carcinoma of Unknown Primary (COUP)
Carcinoma of Unknown Primary (COUP)Carcinoma of Unknown Primary (COUP)
Carcinoma of Unknown Primary (COUP)
 
Ihc
IhcIhc
Ihc
 
Tumour markers with Recent Advances
Tumour markers with Recent AdvancesTumour markers with Recent Advances
Tumour markers with Recent Advances
 
Case 3
Case 3Case 3
Case 3
 
Use of Autoantibodies to detect the onset of breast cancer
Use of Autoantibodies to detect the onset of breast cancerUse of Autoantibodies to detect the onset of breast cancer
Use of Autoantibodies to detect the onset of breast cancer
 
Using biomarkers to monitor the dynamics of tumor
Using biomarkers to monitor the dynamics of tumorUsing biomarkers to monitor the dynamics of tumor
Using biomarkers to monitor the dynamics of tumor
 
Tumor Markers.pptx
Tumor Markers.pptxTumor Markers.pptx
Tumor Markers.pptx
 
Ovariancancer
OvariancancerOvariancancer
Ovariancancer
 
Tumor markers
Tumor markersTumor markers
Tumor markers
 
TUMOR MARKERS OF COLORECTAL CARCINOMA
TUMOR MARKERS OF  COLORECTAL CARCINOMATUMOR MARKERS OF  COLORECTAL CARCINOMA
TUMOR MARKERS OF COLORECTAL CARCINOMA
 
Gynecologic Tumor Markers
Gynecologic  Tumor  MarkersGynecologic  Tumor  Markers
Gynecologic Tumor Markers
 
Diagnostic tools in oncology
Diagnostic tools in oncologyDiagnostic tools in oncology
Diagnostic tools in oncology
 
12- Tumor marker .pdf
12- Tumor marker .pdf12- Tumor marker .pdf
12- Tumor marker .pdf
 
TESTICULAR TUMORS Etiopathogenesis, Features and Treatment
TESTICULAR TUMORS Etiopathogenesis, Features and TreatmentTESTICULAR TUMORS Etiopathogenesis, Features and Treatment
TESTICULAR TUMORS Etiopathogenesis, Features and Treatment
 

Último

Brief introduction to information ecosystem x public health.pptx
Brief introduction to information ecosystem x public health.pptxBrief introduction to information ecosystem x public health.pptx
Brief introduction to information ecosystem x public health.pptxTina Purnat
 
EMBRYOLOGY AND FOETAL DEVELOPMENT-mayu.pdf
EMBRYOLOGY AND FOETAL DEVELOPMENT-mayu.pdfEMBRYOLOGY AND FOETAL DEVELOPMENT-mayu.pdf
EMBRYOLOGY AND FOETAL DEVELOPMENT-mayu.pdfMayuriGamit2
 
TARGET DELINEATION IN RECTUM CANCER BY DR KANHU
TARGET DELINEATION IN RECTUM  CANCER BY DR KANHUTARGET DELINEATION IN RECTUM  CANCER BY DR KANHU
TARGET DELINEATION IN RECTUM CANCER BY DR KANHUKanhu Charan
 
(IDE)and(IVD),QMS,21 CFR part820 , 801)
(IDE)and(IVD),QMS,21 CFR part820  , 801)(IDE)and(IVD),QMS,21 CFR part820  , 801)
(IDE)and(IVD),QMS,21 CFR part820 , 801)chahattyagi200
 
Spinal cord Gross anatomy with Clinical Anatomy.pptx
Spinal cord Gross anatomy with Clinical Anatomy.pptxSpinal cord Gross anatomy with Clinical Anatomy.pptx
Spinal cord Gross anatomy with Clinical Anatomy.pptxsiddharthroy26587
 
Neurological Evaluation of Acute Ischemic stroke in Emergency Room
Neurological Evaluation of Acute Ischemic stroke in Emergency RoomNeurological Evaluation of Acute Ischemic stroke in Emergency Room
Neurological Evaluation of Acute Ischemic stroke in Emergency RoomSudhir Kumar
 
INTRODUCTION TO THE FORENSIC SCIENCE.ppt
INTRODUCTION TO THE FORENSIC SCIENCE.pptINTRODUCTION TO THE FORENSIC SCIENCE.ppt
INTRODUCTION TO THE FORENSIC SCIENCE.pptKavitha Krishnan
 
Thyroid function tests for MBBS, LAB. MED & BDS.pptx
Thyroid function tests for MBBS, LAB. MED & BDS.pptxThyroid function tests for MBBS, LAB. MED & BDS.pptx
Thyroid function tests for MBBS, LAB. MED & BDS.pptxRajendra Dev Bhatt
 
SMA Implementation science seminar (Day 1).pptx
SMA Implementation science seminar (Day 1).pptxSMA Implementation science seminar (Day 1).pptx
SMA Implementation science seminar (Day 1).pptxAbdirahmanWaseem
 
Routine Medicine Laboratory Testing _ CÁC XÉT NGHIỆM THƯỜNG QUY ÁP DỤNG TRON...
Routine Medicine Laboratory Testing  _ CÁC XÉT NGHIỆM THƯỜNG QUY ÁP DỤNG TRON...Routine Medicine Laboratory Testing  _ CÁC XÉT NGHIỆM THƯỜNG QUY ÁP DỤNG TRON...
Routine Medicine Laboratory Testing _ CÁC XÉT NGHIỆM THƯỜNG QUY ÁP DỤNG TRON...DUY NGUYEN PHUC
 
Ortho Products Franchise-solace biotech limited
Ortho Products Franchise-solace biotech limitedOrtho Products Franchise-solace biotech limited
Ortho Products Franchise-solace biotech limitedSBL DIGITAL
 
Methicillin-resistant Staphylococcus Aureus (MRSA)
Methicillin-resistant Staphylococcus Aureus (MRSA)Methicillin-resistant Staphylococcus Aureus (MRSA)
Methicillin-resistant Staphylococcus Aureus (MRSA)Ahmad Thanin
 
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on time
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on timeTracheostomy .pdf ENT by QuickMedTALK. getting things done on time
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on timeQuick MedTalk
 
Explaining "pathology" in digital pathology
Explaining "pathology" in digital pathologyExplaining "pathology" in digital pathology
Explaining "pathology" in digital pathologyYves Sucaet
 
Neutraceuticals, Herb-drug & Herb-food inetractions
Neutraceuticals, Herb-drug & Herb-food inetractionsNeutraceuticals, Herb-drug & Herb-food inetractions
Neutraceuticals, Herb-drug & Herb-food inetractionsPradnya Wadekar
 
The Art and the Science of UK General Practice A historical review and timeli...
The Art and the Science of UK General Practice A historical review and timeli...The Art and the Science of UK General Practice A historical review and timeli...
The Art and the Science of UK General Practice A historical review and timeli...JakeMatthews12
 
Human Skeletal System_By Anupam Das......
Human Skeletal System_By Anupam Das......Human Skeletal System_By Anupam Das......
Human Skeletal System_By Anupam Das......anupamdas2143
 
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptx
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptxNECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptx
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptxSizan Thapa
 
Range of Secondary Electrons and Electron Build-Up: Impact on Scatter in Homo...
Range of Secondary Electrons and Electron Build-Up: Impact on Scatter in Homo...Range of Secondary Electrons and Electron Build-Up: Impact on Scatter in Homo...
Range of Secondary Electrons and Electron Build-Up: Impact on Scatter in Homo...Dr. Dheeraj Kumar
 
airway management recorded for S2.pptx
airway management  recorded  for S2.pptxairway management  recorded  for S2.pptx
airway management recorded for S2.pptxnakera38
 

Último (20)

Brief introduction to information ecosystem x public health.pptx
Brief introduction to information ecosystem x public health.pptxBrief introduction to information ecosystem x public health.pptx
Brief introduction to information ecosystem x public health.pptx
 
EMBRYOLOGY AND FOETAL DEVELOPMENT-mayu.pdf
EMBRYOLOGY AND FOETAL DEVELOPMENT-mayu.pdfEMBRYOLOGY AND FOETAL DEVELOPMENT-mayu.pdf
EMBRYOLOGY AND FOETAL DEVELOPMENT-mayu.pdf
 
TARGET DELINEATION IN RECTUM CANCER BY DR KANHU
TARGET DELINEATION IN RECTUM  CANCER BY DR KANHUTARGET DELINEATION IN RECTUM  CANCER BY DR KANHU
TARGET DELINEATION IN RECTUM CANCER BY DR KANHU
 
(IDE)and(IVD),QMS,21 CFR part820 , 801)
(IDE)and(IVD),QMS,21 CFR part820  , 801)(IDE)and(IVD),QMS,21 CFR part820  , 801)
(IDE)and(IVD),QMS,21 CFR part820 , 801)
 
Spinal cord Gross anatomy with Clinical Anatomy.pptx
Spinal cord Gross anatomy with Clinical Anatomy.pptxSpinal cord Gross anatomy with Clinical Anatomy.pptx
Spinal cord Gross anatomy with Clinical Anatomy.pptx
 
Neurological Evaluation of Acute Ischemic stroke in Emergency Room
Neurological Evaluation of Acute Ischemic stroke in Emergency RoomNeurological Evaluation of Acute Ischemic stroke in Emergency Room
Neurological Evaluation of Acute Ischemic stroke in Emergency Room
 
INTRODUCTION TO THE FORENSIC SCIENCE.ppt
INTRODUCTION TO THE FORENSIC SCIENCE.pptINTRODUCTION TO THE FORENSIC SCIENCE.ppt
INTRODUCTION TO THE FORENSIC SCIENCE.ppt
 
Thyroid function tests for MBBS, LAB. MED & BDS.pptx
Thyroid function tests for MBBS, LAB. MED & BDS.pptxThyroid function tests for MBBS, LAB. MED & BDS.pptx
Thyroid function tests for MBBS, LAB. MED & BDS.pptx
 
SMA Implementation science seminar (Day 1).pptx
SMA Implementation science seminar (Day 1).pptxSMA Implementation science seminar (Day 1).pptx
SMA Implementation science seminar (Day 1).pptx
 
Routine Medicine Laboratory Testing _ CÁC XÉT NGHIỆM THƯỜNG QUY ÁP DỤNG TRON...
Routine Medicine Laboratory Testing  _ CÁC XÉT NGHIỆM THƯỜNG QUY ÁP DỤNG TRON...Routine Medicine Laboratory Testing  _ CÁC XÉT NGHIỆM THƯỜNG QUY ÁP DỤNG TRON...
Routine Medicine Laboratory Testing _ CÁC XÉT NGHIỆM THƯỜNG QUY ÁP DỤNG TRON...
 
Ortho Products Franchise-solace biotech limited
Ortho Products Franchise-solace biotech limitedOrtho Products Franchise-solace biotech limited
Ortho Products Franchise-solace biotech limited
 
Methicillin-resistant Staphylococcus Aureus (MRSA)
Methicillin-resistant Staphylococcus Aureus (MRSA)Methicillin-resistant Staphylococcus Aureus (MRSA)
Methicillin-resistant Staphylococcus Aureus (MRSA)
 
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on time
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on timeTracheostomy .pdf ENT by QuickMedTALK. getting things done on time
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on time
 
Explaining "pathology" in digital pathology
Explaining "pathology" in digital pathologyExplaining "pathology" in digital pathology
Explaining "pathology" in digital pathology
 
Neutraceuticals, Herb-drug & Herb-food inetractions
Neutraceuticals, Herb-drug & Herb-food inetractionsNeutraceuticals, Herb-drug & Herb-food inetractions
Neutraceuticals, Herb-drug & Herb-food inetractions
 
The Art and the Science of UK General Practice A historical review and timeli...
The Art and the Science of UK General Practice A historical review and timeli...The Art and the Science of UK General Practice A historical review and timeli...
The Art and the Science of UK General Practice A historical review and timeli...
 
Human Skeletal System_By Anupam Das......
Human Skeletal System_By Anupam Das......Human Skeletal System_By Anupam Das......
Human Skeletal System_By Anupam Das......
 
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptx
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptxNECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptx
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptx
 
Range of Secondary Electrons and Electron Build-Up: Impact on Scatter in Homo...
Range of Secondary Electrons and Electron Build-Up: Impact on Scatter in Homo...Range of Secondary Electrons and Electron Build-Up: Impact on Scatter in Homo...
Range of Secondary Electrons and Electron Build-Up: Impact on Scatter in Homo...
 
airway management recorded for S2.pptx
airway management  recorded  for S2.pptxairway management  recorded  for S2.pptx
airway management recorded for S2.pptx
 

Immunohistochemistry is an important complimentary tool for diagnosis of cancer"

  • 1. “ IHC is an Important Complimentary Tool for Diagnosis of Cancer” Lawrence T. Richards M.S.,H.T(ASCP), QIHC(ASCP) Consultant, Bio Marker Assay Development, Santa Barbara, California. For teaching purpose only
  • 2. “ The Diagnostic Power of any Immunohistochemical Procedure is no Greater than the wisdom of the Pathologist interpreting it.” Dr.Allen M.Gown
  • 3. IHC as a compliment to H&E • Is H&E alone not enough? • Is Special Stain not enough? • Is IHC alone enough?
  • 4. Special Stain Antibody for Yeast Budding yeast GMS Stain and H&E (Blastomycosis). AFB HP Alcian YellowToluidine Blue
  • 5. Special stain vs IHC H.pylori Alcian Yellow-Toluidine Blue H.Pylori antibody
  • 7. Usefulness of IHC tests. • Poorly differentiated tumors and mixed carcinomas • Undifferentiated tumors of unknown origin • Treatment based on sub-type of cancer: Personalized Medicine eg., Breast Ca • Monitoring progress of cancer (Predictive and Prognosis) • In Malignant Lymphoma, • In identifying Carcinoid (Neuroendocrine) tumors • In Cytologic specimens
  • 8. IHC helps in deciding Treatments ER/PR About 75% of all breast cancers are “ER positive.” They grow in response to the hormone estrogen. About 65% of these are also “PR positive.” They grow in response to another hormone, progesterone. If your breast cancer’s cells have a significant number of receptors for either estrogen or progesterone, your cancer is considered hormone-receptor positive and likely to respond to endocrine therapies Breast cancer tumors that are ER/PR-positive are 60% likely to respond to endocrine therapy. Tumors that are ER/PR negative are only 5% to 10% likely to respond to endocrine therapy Her2 In about 20% to 25% of breast cancers, the cancer cells make too much of a protein known as HER2/neu. These breast cancers tend to be much more aggressive and fast-growing. For women with HER2-positive breast cancers, the drug Herceptin has been shown to dramatically reduce the risk of recurrence Triple Negative Some breast cancers -- estimates range between 10% and 17% -- are known as “triple negative” because they lack estrogen and progesterone receptors and do not overexpress the HER2 protein. The majority of breast cancers associated with the breast cancer gene known as BRCA1 are triple negative. These cancers generally respond well to adjuvant chemotherapy http://www.webmd.com/breast-cancer/breast-cancer-types-er-positive-her2-positive
  • 10. Histiogenic Dx of Neoplasm • ID of proliferation of cells Epithelium NeuroEndocrine Melanocyte A) Expression of cytokeratin AE1/AE3 in lung carcinosarcoma ; B) chromogranin expression in gastric neuroendocrine carcinoma ; C) HMB 45 immunostainning in melanoma .
  • 12. Metastatic Adenocarcinoma of unknown origin with site specific markers PSA (-) + TTF-1 (-) + GCDFP15 + (-) CDX2 / CK20 Colon Lung CDX2 CK 7 Mesothelin (-) + (-) + Mesothelin (-) + Lysozyme + (-) CA125 + (-) (-) + ER MC5+ (98%) Prostate + Breast Stomach/Pancreas + (-) Ovary (-) Breast Pancreas,(Ovary serous) Stomach / Pancreas Stomach / Pancreas Breast / Stomach / Pancreas Source: www.clincancerres.aacrjournals.org/egi/content/full/11/10/3766 Colon
  • 13. Endocervical Ad.Ca & Endometrial Mucinous Ad.Ca ECA • • • • MUC-1(-) ER(-) PR(-) P16(+) EMMA • • • • MUC-1 (+) ER(+) PR(+) P16(-) Khoury T et al.BMC Clin Path 2006;6:1
  • 14. Prostate Ca or Benign ? • Prostate Cancer • • • • • • • • EpCam + ATM + AMACR + PSA + / (-) 34ßE12 (-) almost all p63 (-) almost all Prostein + NKX3.1 + • Benign Prostate • • • • • • • • EpCam (-) ATM (-) / + AMACR (-) PSA + / (-) 34ßE12 + p63 + Prostein + NKX3.1 + ATM=ataxia-telangiectasia mutated;AMACR=alpha-methylacyl-CoA racemase;Ep-Cam=epithelial transmembrane glycoprotein Hammerich KH et al.Application of Immunohistochemistry to the Genitourinary System(Prostate, Urinary Bladder, Testis, and Kidney)Archives of Pathology and Laboratory Medicine;132:432-440,2007
  • 15. Urothelial Ca vs Prostate Ca Urothelial ca • • • • • • • • • • EMA CK7 P63 CK5/6 EpCam CD57 PSA PAP NKX3.1 Prostei n Prostate ca + + +/0 +/0 +/0 -/+ +/0 + 0 +/0 + 0 + 0 + Hammerich KH.Archives of Pathology and Laboratory Medicine;132(3):432-440 Urothelial ca Prostate ca
  • 16. Prognastic Risk Biomarkers (or screening biomarkers) Describe risk of cancer occurrence or cancer progression because they are implicated in neoplastic progression and include: 1. Genetic predisposition (e.g., BRCA1/2) 2. Over expression of genes (e.g., BCRABLTyrosin Kinase Inhibitor in CML, HER-2/neu in Br Ca,PTEN, RAS,Colo Rectal Cancer AKTin Pancreatic cancer) 4.Environmental factors and lifestyle (e.g., HPV or HBV infection http://www.esmo.org/content/download/8713/176680/file/ The-use-of-Biomarkers-for-Treatment-Sessa-Fasolo.pdf
  • 17. Undifferentiated Tumors Use of IHC to differentiate broad lineage Pan CK AE1/AE3 CD45 (LCA) HMB45 or S100 VIM Carcinoma Positive Negative Negative Negative Melanoma Negative Negative Positive Sarcoma Negative Negative Negative Positive Lymphoma Negative Positive Positive Negative Negative
  • 18. Carcinoma Use of CK7 and CK20 CK7 + CK20 + CK7 + CK20 - CK7 – CK20 + CK7 – CK20 - Urothelial Ca Pancreatic Ad Ca OvarianMucinous Ca Ad Ca of Bladder Gastric Ad Ca Cholangio Ca subset Breast Ca EndoMetrial Ad Ca EndoCervical Ad Ca Ovarian Cerous Ca Lung Ad Ca Cholangio Ca LungSmCC Mesothelioma Thyroid Ca SCC of Cervix SalivaryGland tumors Urothelial Ca subset Pancreatic and Gastric Ad Ca subset Colorectal Ad Ca Markel Cell ca Gastric Ad Ca subset Prostate Ad Ca SCC RCC HCC Mesothelioma AdrenoCortical ca NonSeminoma LungSmCC minorSubset Gastric Ad Ca subset http://www.pathinformatics.com/department/documents/SusanE%20Lecture.pdf
  • 19. Immunohistochemistry stains in squamous cell carcinoma and adenocarcinoma of lung. H&E: hematoxylin and eosin; CK: cytokeratin; TTF-1: thyroid transcription factor 1. Squamous carcinomas are typically positive for CK5/6 and P63, and negative for CK7 and TTF-1, with the reverse profile for adenocarcinoma although this case of squamous cell carcinoma demonstrates focal weak staining for CK7. SqCC AdCa “Ancillary Testing in Lung Cancer Diagnosis” Dublinski et al. Openi.nlm.nih.gov
  • 20. Primary and Additional Markers For teaching purpose only For teaching purpose only
  • 21. CK7 and CK20 For teaching purpose only http://www.pathinformatics.com/department/documents/SusanE%20Lecture.pdf
  • 22. Metastatic AdenoCarcinoma from Unknown Primary Tumors from Unknown Primary Site http://www.translational-medicine.com/content/pdf/1479-5876-10-12.pdf For teaching purpose only
  • 23. CUP Diagnosis (Cancer of Unknown Primary) For teaching purpose only http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631214/figure/f1-gcr1_6p0229/
  • 24. Prostate Ca vs Urothelial Ca Cancer PSA/ CKPSAP hmw CK7 CK20 Prostate + Adenoca few - few + foc + foc + Urothelial Ca + few - + rare - +/- CK17 T -Mod CEAm CD57 Leu 7 6%+ - foc + + few - +/- + 60-90% foc + http://www.ihcworld.com/_newsletter/2001/focus_mar_2001.pdf + few-
  • 25. Immunoperoxidase Panel for Liver Lesions Hepatocellular Colon Biliary Pancreas Ovary /EM Sarcoma Hepar + - - - - - AFP + - - - - - CEA - + + +/- +/- - CK7 - - + + + - CK20 - + ? ? - - AE1 AE3 +/- + +/- + + - CA 19-9 - - - + - - ER + (Not for Renal Cell Carcinoma). (?) suggests could be positive 35% to 65% or negative); and +/- dependent on subtype of histology from that organ. -
  • 26. Napsin A + TTF-1 Napsin A, an aspartic acid protease whose expression in the lung is regulated by TTF-1, has also shown promise in helping to differentiate primary lung from metastatic adenocarcinomas. While Napsin A expression may also be seen in normal kidney and in a proportion of renal tumors, positivity for both TTF-1 and napsin A is a strong indication that an adenocarcinoma originated from lung .
  • 27. Examples of common panels of Antibodies Used Generic T-cell Vs B-Cell : CD3, CD20, CD45 Folicular Lymphoma Vs Hyperplasia: Bcl2, Bcl6, CD3, CD10,CD20 Low Grade B Lymphoma: CD3, CD5, CD10, CD20, CD23, CD43, Bcl2, Bcl6, MALT Lymphoma: CD3, Cd5, CD20, Bcl2, ISH Kappa and Lambda Hodgkin’s Lymphoma: CD3, CD15, CD20, CD30, CD45 Myeloma: CD138, ISH Kappa and Lambda Carcinoma Vs Lymphoma: CD3, CD20, CD45, PanCK Metastatic Carcinoma: CK7, CK20, TTF-1 GIST: CD117, CD34, S100, Desmin, SMA Mesothelioma: PanCK, CK5/6, Calret, TTF-1, CEA, CD15 If male add PSA/ if female add BRST2
  • 28. Antibodies commonly used • Breast ER, PR, gross cystic fluid protein, CK7,CK20, E-cadherin • Colon and other GI tract CEA (monoclonal), CK7, CK20 • Germ cell PLAP, -fetoprotein, -HCG, AE1/3 • Hepatocellular Hepar, -fetoprotein, CK7, CK20, AE1 and AE3 (separately) • Lung TTF-1, CK7, CK20, CEA, Ber-EP4, chromogranin, synaptophysin, S100 • Lymphoma LCA (CD45RB monoclonal), CD3, CD20, CD30, ALK-1, myeloperoxidase, and light chains, Bcl-2
  • 29. Antibodies commonly used contd. • Mesothelioma: Calretinin, AE1, AE3 • Melanoma: S100 (when spindled cells), HMB-45 • • • • • • • (when epithelioid), MART1 Neuroendocrine : Chromogranin, synaptophysin, NSE Pancreas : AE1/3, CK7, CK20, CA 19-9, CEA, chromogranin, synaptophysin, -antichymotrypsin, CD10, PR, Ber-EP4 Prostate :PSA, CK7, CK20 Renal: EMA, CD10, HMB-45, inhibin- (to exclude adrenal /cortical) Sarcoma : Vimentin, S100, CD117 (c-Kit), CD34,SMA, myogenin, CD31, CD68, desmin,CD1a, CD99 Thyroid: TTF-1, thyroglobulin, calcitonin, CEA Urothelial : CK7, CK20,Uroplakin
  • 30. Conclusion Thank you for giving me an opportunity to share my knowledge with you all. It is my hope that that this presentation will fulfill the goal of providing the attendees a little insight into the powerful tool of IHC in diagnosis of difficult cases and help in monitoring disease progression in patients and course correction in treatment procedures.
  • 31. Acknowledgements New York University -Department of Environmental Medicine DAKO -Research and Development Quest Diagnostics -Clinical Trials and Bio-Marker Development

Notas do Editor

  1. When morphology and routine staining cannot provide all the diagnostic answers, pathologists turn to advanced staining techniques like Special Stains, Immunohistochemistry (IHC)  and In Situ Hybridization (ISH).
  2. Immunohistochemistry has become the “Gold Standard” for many diagnostic situations. However, the vast majority of cases do not require any additional stains other than the H & E. or special Stains. In the words of Dr.Rodney Miller : “….a Pathologist must be committed to remaining current with ever-expanding IHC literature, since awareness of the specificities of the antibodies and expected patterns of reactivity in tissue is critical to employ this technique effectively and avoid diagnostic or interpretive errors.”.
  3. In most cases YES. But we need all three. Special stains and IHC both compliment H&E in making the correct diagnosis. In the following few slides I will show cause why and how special stain and IHC compliment H&E and then I will move on to Immunohistochemistry and panels in diagnosis of cancer.
  4. Special stains remain an important tool for many Pathologists providing a powerful complement to H&E. Micro-organisms are easily and clearly identified using Special Stains than with IHC.
  5. Special stain gives a better contrast and morphology of the spirochetes than IHC.
  6. Adenocarcinoma stained with special Stain and MUC-1
  7. When Pathologists come across a case of poorly differentiated carcinoma or undifferentiated carcinoma of unknown origin, an additional test like special stains or IHC or both is necessary for a correct diagnosis of the disease. IHC is also very useful when it is important to know the sub-type of the cancer for selecting the drug of choice or to monitor treatment based on the progress of the disease. 1) Sometimes it is difficult to identify if the tumor is from epithelial or from connective tissues or from plasma cells or lymphatic or from mixed cell types. IHC is very useful in these cases to identify if it is a carcinoma or sarcoma or lymphoma or mixed like carcinosarcoma or adeno-squamous carcinoma etc 2) IHC is a reliable tool in deciding if the tumor originated as a primary or it is metastatic from another organ. 3)In Treatments: BRCA1,BRCA2 for Hereditary BrCa, Her2 for Herceptin treatment, BCR for CML(Gleevac) 4) IHC play an increasingly important role in the clinical management of breast cancer(ER,Ki67),VEGF in Melanoma, P63 in Head and neck cancer. 5) without IHC it is difficult to diagnose correctly any Hematolymphoid proliferations. http://www.pathologyportal.org/96th/pdf/companion02h03.pdf 6)However PSAP will stain carcinoid tumors of unknown origin so should not conclude that it is from prostate. If you include an nuero endocrine group antibody you will get the correct Dx 7) Intraoperative SLN evaluation by imprint cytology with immunohistochemistry achieves a more accurate diagnosis of metastasis than imprint cytology alone
  8. These classifications provide doctors with valuable information about how the tumor acts and what kind of treatments may work best. In general, surgical and radiation treatments are similar for these different types of breast cancer. But drug treatments -- such as chemotherapy, endocrine therapies, and other medications -- are usually different. These treatments are targeted to the specific type of cancer.
  9. Markers for Tissue of origin
  10. The immunohistochemical reactions can be used in different situations within research or pathological anatomy laboratories. The most important are: 1) histogenetic diagnosis of morphologically non-differentiated neoplasias ; 2) subtyping of neoplasias (such as lymphomas, for example); 3) characterization of primary site of malignant neoplasias; 4) research for prognostic factors and therapeutic indications of some diseases; 5) discrimination of benign versus the malignant nature of certain cell proliferations ; identification of structures, organisms and materials secreted by cells.
  11. An Algorithm can be designed broadly or based on information available to the Pathologist about the patient he or she can design a simple algorithm to R/O some doubts and confirm some Dx.
  12. <number> Example of most common -Applying this panel and the algorithm correctly classified 88% of the original known tumors.(352 known Ad ca were used)However,HCC expressed none of these markers. If you do TTF-1 first then remember that TTF-1 will show cytoplasmic reactivity in a granualr pattern in most of Prostate Ad Ca. True staining should be Nuclear. Some tumors had similar profiles that were difficult to separate: pancreas and stomach (but we can say with some degree of confident that if CK7 is negative ca of pancreas unlikely, CA 125 pos and mesothelin pos then more likely pancreas. ER,mesothelin and CA125 together indicate ovary.Cocktails: Mammaglobin + ER is good cocktail for br ca. MC5 + will increase the specificity upto 98% Explanation: GCDFP 15 +, CDX2 (-), at this stage if we do MC5 and if that is positive then we can say with 98% certainity that the primary tumor is breast. Here is another scenario: GCDFP15(-), CDX2(-),ER + BUT Mesothelin (-) = Breast.
  13. <number> Dx difficult when tumor involves the lower uterine segmnt or upper endocx.It becomes more difficult in the mucinous subtype in which stroma is absent, (one of the feature that suggests an EM origin). This differentiation is very important due to its clinical significance,that is their differences in management of the disease and prognosis. While the treatment of EM ca starts with surgical staging and intraoperative assessment of the grade and extent of tumor in the uterus, primary ECA is treated by an initial radical hysterectomy and pelvic lymph adenectomy with or without adjuvant radiation. All four ab as a panel gives 100% differential Dx. However any two markers MUC1 and p16, MUC1 with ER/PR also gives best results. You can include Vim also EMMA(70%) and ECA(7%)
  14. <number> Panel of Abs is very useful when you have a dilemma to treat or not decision to make in a not so sure diagnosis. Is it BPH (Benign Prostatic Hyperplasia? Or PIN Prostate Intra epithelial Neoplsm - a precursor to Prostate cancer?
  15. <number> In most cases of a poorly differentiated carcinoma within the area of prostate/urinary bladder, morphological features on the H & E alone is sufficient. However if overlapping morphologic features of both neoplsms are present, making determination of site of origin is very difficult and may necessitate IHC confirmation.
  16. For example: BRCA1/2 predisposes to Breast cancer.Over expression of HER2/neu in 30% of Breast cancer patients, amplification of RAS in colorectal cases and over expression and suppression of PTEN vs AKT in cancer modulations. Presence of HPV in Head and neck Sq.Cell Carcinoma and Genital warts and cervical cancer. CML-Chronic Myelogenous Leukemia results in Philadelphia Chromosome(http://www.nejm.org/doi/full/10.1056/NEJMct071828 Drug: Imatinib CRC:ColoRectal Cancer
  17. PanCK(AE1/AE3) can detect most of carcinoma. CD45 will be positive for 95% of Lymphoma, mMelanoma will be 95 to 100% positive with HMB45. There are a few exemptions to the above. However, PanCK is positive for Gilial Tumors and Schwanoma and mesenchymal tumors. And..Negative for Hepato Cellular Carcinoma. PanCK is also positive for mixed tumors like Sarcomatoidcarcinoma. In Renal Cell carcinoma, Endometrial adenoCarcinoma, Ovarian carcinoma and Thyroid carcinoma, Vimentin is co-expressed with Cytokeratins.
  18. Expression of CK7 and CK20 can differentiate most of Carcinoma from each other.
  19. Sq CC Vs AdCa
  20. Primary and Addl Markers
  21. However each group can be further differentiated by using specific Antibodies for each disease. (Please refer to hand out for details). Algorithmic immunohistochemical analysis of undifferentiated carcinomas. CA indicates carcinoma; adenoCA, adenocarcinoma; SmCC, small cell carcinoma; SCC, squamous cell carcinoma; RCC, renal cell carcinoma; HCC, hepatocellular carcinoma; ¶, seminoma is keratin negative, OCT3/4 positive; *NE markers, neuroendocrine markers, including synaptophysin, chromogranin, and CD56; , undifferentiated anaplastic thyroid carcinoma is often negative for thyroid transcription factor 1 (TTF-1) and thyroglobulin; and , characteristic canalicular pattern.
  22. Here is another algorithm. As you can see most of the antibodies used are common ones routinely used in cancer diagnosis. Diagnostic algorithm to characterize metastatic adenocarcinoma from unknown primary. (CK: cytokeratin; TTF1: thyroid transcription factor 1; ER: estrogen receptor; CA125: cancer antigen 125; tireo: tireoglobulin; VIM: vimentin; PSA: prostate specific antigen)
  23. With the help of IHC as a tool in diagnosis 90% of cancer can be correctly guessed.
  24. KEY: + (few -) = Large majority of cases positive, a few negative cases may be seen - (foc +) = Largely negative, but scattered positive tumor cells may be seen +/- = Tumor may be either positive or negative + (rare-) = Tumor positive, but rare negative cases may be encountered
  25. Liver Lesion panel
  26. J. Ye, J. J. Findeis-Hosey, Q. Yang et al., “Combination of napsin A and TTF-1 immunohistochemistry helps in differentiating primary lung adenocarcinoma from metastatic carcinoma in the lung,” Applied Immunohistochemistry and Molecular Morphology, vol. 19, no. 4, pp. 313–317, 2011.
  27. Hodgekin’s:NLPHL with LCA+, CD20+, EMA+/-, EBER – z CHL with a LCA -, CD30+, CD15+, EBER+/-
  28. Breast ER, + or - PR, + or - GCDFP ;gross cystic fluid protein, 75 to 95% + CK7, CK20 + or – from Colon or Lung E-cadherin + DCIS and - ILC http://www.webmd.com/breast-cancer/breast-cancer-types-er-positive-her2-positive Lung: Ber-EP4 + reactive mesothelial cells from cancer cells.
  29. I thank NYU for giving me an opportunity to work on Immunohistochemistry from its infant stages (1984 …) I thank DAKO for hiring me to develop new antibodies which were flooding the market after completion of human genome mapping. I also thank Quest Dx for asking me to join their Clinical Trial team for Bio-Marker assay development for leading Bio Pharmas like Pfizer, Scherring-Plough, Merck, Astra-zenka, Biogen-Idec, Roche etc etc
  30. <number>