clinical chemistry

1. Clinical Chemistry
HCM 2219
Dr. Munyekenye

2. Tumor markers
• Definition of terms
• Adenocarcinoma: A carcinoma derived rom
glandular tissue.
• Apha fetoprotein (AFP): A plasma protein produced
by the fetal liver, yolk sac, and gastrointestinal tract;
serum levels decline markedly by the age of one year
but are again elevated in many hepatocellular
carcinomas and teratocarcinomas and embryonal cell
carcinomas.

3. Tumor markers
• Benign prostatic hyperplasia (BPH) :A noncancerous
enlargement of the prostate gland.
• Blood group antigen: Antigen containing a major
carbohydrate component usually found on the surface
of cells or secreted by cells.
• Cancer: A relative autonomous growth of tissue.
• Cancer staging: The process by which cancer is
divided into groups of early and late disease; useful
for prognosis and for guiding therapy.

4. Tumor markers
• Carbohydrate markers: Carbohydrate-related tumor
markers may be (1) antigens on the tumor cell surface
or (2) secreted by the tumor cells.
• Carcinoembryonic antigen (CEA): A glycoprotein
secreted into the glycocalyx coating the luminal
surface of gastrointestinal epithelia.
• Carcinogen: Any cancer-producing substance.
• Carcinoma: A malignant new growth made up of
epithelial cells tending to infiltrate the surrounding
tissues and give rise to metastases.
• Chronic myelocytic leukemia (CML): Chronic
leukemia characterized by granular leukocytes.

5. Tumor markers
• Digital rectal examination (DRE): A technique used
for the for early detection of prostate cancer. It is
performed by inserting a gloved, lubricated finger
into the rectum and feeling for abnormalities.
• Ectopic syndrome: Production of a hormone by
nonendocrine cancerous tissue that normally does not
produce the hormone (e.g., ACTH production by
small-cell lung carcinoma).
• Fluorescence in situ hybridization (FISH): An in situ
hybridization technique in which DNA probes are
labeled with fluorescent tags and hybridized to DNA
to identify and localize specifc sequences.

6. Tumor markers
• Gleason Score: A grading system used to help evaluate the
prognosis of men with prostate cancer.
• Lymphoma :Any neoplastic disorder of the lymphoid tissue.
• Medullary thyroid cancer (MTC): A slow-growing tumor
associated with multiple endocrine neoplasia (MEN)
syndromes.
• Metastasis: The spread of cancer from one part of the body to
another.
• Oncofetal antigen: Protein produced during fetal life that
decreases to low or undetectable levels after birth; reappears in
some forms of cancer as the result of reactivation of genes in
transformed malignant cells.
• Oncogene: A mutated normal cellular gene (proto-oncogene)
that causes the malignant transformation of normal cells when
activated.

7. Tumor markers
• Prognosis: A prediction of the future course and outcome of a
patient’s disease based on currently known indicators (e.g., age,
sex, tumor stage, tumor marker level).
• Receiver operating characteristic (ROC) curve: A plot of
sensitivity versus 1 minus specifcity, or the true-positive rate
versus the false-positive rate; it allows one to pinpoint the
decision cut point at which optimal sensitivity and specifcity can
be achieved.
• Tumor marker: A substance produced by a tumor found in blood,
body f uids, or tissue that may be used to predict the presence
and size o the tumor and monitor its response to therapy.
• Tumor-suppressor gene: A gene involved in the regulation of
cellular growth; loss of a tumor-suppressor gene has the
potential to allow autonomous growth.

8. Tumor markers
• Def: A tumor marker is a substance produced by a
tumor or by the host in response to a tumor, which is
used (1) to differentiate a tumor from normal tissue,
or (2) to detect the presence of a tumor based on
measurements in the blood or secretions.
• Such substances are found in cells, tissues, or body
fluids and are measured qualitatively or quantitatively
by chemical, immunological, or molecular biological
methods.
• Morphologically, cancer tissue has been recognized
by pathologists as resembling fetal tissue more than
normal adult differentiated tissue

9. Tumor markers
• Tumors are graded according to their degree of
differentiation as (1) well differentiated, (2) poorly
differentiated, or (3) anaplastic (without form).
• Tumor markers are the biochemical or immunological
counterparts of the differentiation state of the tumor.
• In general, some tumor markers represent re-
expression of substances produced normally by
embryogenically closely related tissue.
• Some tumor markers are associated with one type of
cancer; others are seen in several cancer types

10. Tumor markers
• Many of the better-known markers are also seen in
noncancerous conditions.
• Consequently, these tumor markers are not diagnostic
for cancer.
• It is thought that the concentration of tumor markers in
blood reflects tumor activity and volume.
• Clinically, an ideal tumor marker should be both
specifc for a given type of cancer and sensitive enough
to detect small tumors for early diagnosis or during
screening.

11. Tumor markers
• A simple defnition of cancer is a relatively
autonomous growth of tissue.
• Others define cancer as “a term used for diseases in
which abnormal cells divide without control and are
able to invade other tissues. Cancer cells can spread
to other parts o the body through the blood and lymph
systems.”
• Common to all of the definitions is the concept of
autonomous and abnormal cell growth.

12. Clinical application of tumor markers
• In general, tumor markers may be used:
• (1) For diagnosis, prognosis, and prediction
• (2) For monitoring the effects of therapy and
• (3) As targets for localization and therapy.
• Ideally, a tumor marker should be produced by tumor
cells and should be detectable in body fluids.
• It should not be present in healthy people or in benign
conditions

13. Enzymes
• Enzymes were one of the first groups of tumor markers to
be identified.
• Their elevated activities were used to indicate the
presence of cancer.
• Their measurement is done using spectrophotometry to
determine enzymatic activities.
• With few exceptions, an increase in the activity or mass of
an enzyme or isoenzyme is not specifc nor sensitive
enough to be used to identify the type of cancer or the
specific organs involved.
• There fore, enzymes are most suitable as nonspecific
tumor markers.
• Elevated enzymes may signal the presence of malignancy.

14. Alkaline phosphatase
• (1) Liver, (2) bone, and (3) placenta are primary sources
o
• alkaline phosphatase (ALP).
• The ALP in the sera of normal adults is derived
primarily rom the liver or biliary tract.
• Elevated ALP is seen in primary or secondary liver
cancer.
• Greatest elevations are seen in patients with osteoblastic
lesions, such as those with prostatic cancer with bone
metastases.
• In liver metastases, serum ALP shows a better
correlation with the extent of liver involvement than do
the results of other liver function tests.

15. ALP
• Placental alkaline phosphatase (PALP) is synthesized
by the trophoblast and is elevated in the sera o
pregnant women.

16. Lactate dehydrogenase
• Lactate dehydrogenase (LD) is an enzyme in the
glycolytic pathway that is released as the result of cell
damage.
• Elevation of LD in malignancy is rather nonspecific.
• It has been demonstrated in a variety of cancers,
including (1) liver cancer, (2) non-Hodgkin’s lymphoma,
(3) acute leukemia, (4) nonseminomatous germ cell
testicular cancer, (5) seminoma, and (6) neuroblastoma;
and in (7) other carcinomas, such as breast, colon,
stomach, and lung cancer.
• Serum LD has been shown to correlate with tumor mass
in solid tumors and provides a prognostic indicator for
disease progression.

17. Frequently ordered Tumor markers
• Alpha (α) Fetoprotein: AFP is an abundant serum protein
normally synthesized by the fetal liver that is reexpressed
in certain types of tumors.
• This reexpression during malignancy classifies AFP as a
carcinoembryonic protein.
• AFP is often elevated in patients with hepatocellular
carcinoma (HCC) and germ cell tumors.
• AFP is used for the diagnosis, staging, prognosis, and
treatment monitoring of HCC.
• Also known as hepatoma, HCC is a tumor that originates
in the liver, often due to chronic diseases, such as
hepatitis and cirrhosis.

18. Frequently ordered Tumor markers
• AFP has a sensitivity ranging from 40% to 65% and
specificity of 80% to 95% (at cutoffs ranging from 20
to 30 ng/mL).
• Very high levels of AFP (>500 ng/mL) in high risk
individuals are considered diagnostic of HCC.
• AFP is measured using any of a variety of
commercially available automated immunoassays.
• These are typically sandwich immunoassays relying on
monoclonal or polyclonal antibodies directed toward
different regions of AFP

19. Frequently ordered Tumor markers
• Cancer antigen 125: CA-125 may be useful for detecting
ovarian tumors at an early stage
• Although it is not usually found in serum, CA-125 may
be elevated in patients with endometriosis, during the
first trimester of pregnancy, or during menstruation.
• CA-125 is a serologic marker of ovarian cancer.
• As with most other tumor markers, CA-125 should not
be used to screen for ovarian cancer in asymptomatic
individuals.
• CA-125 can be detected by immunoassays.

20. Frequently ordered Tumor markers
• Carcinoembryonic antigen: CEA is a prototypical example
of an oncofetal antigen.
• It is expressed during development and then reexpressed in
tumors.
• CEA is the most widely used tumor marker for colorectal
cancer and is also frequently elevated in lung, breast, and
gastrointestinal tumors.
• CEA can be used to aid in the diagnosis, prognosis, and
therapy monitoring of colorectal cancer.
• Although high levels of CEA (>10 ng/mL) are frequently
associated with malignancy, high levels of CEA are not
specific for colorectal cancer, and therefore, CEA is not
used for screening.

21. Frequently ordered Tumor markers
• Because of its role in cell adhesion, CEA has been
postulated to be involved in metastasis.
• Like other serologic tumor markers, CEA may be
elevated nonspecifically because of impaired clearance
or through increased production.
• Increased CEA concentrations have been observed in
heavy smokers and in some patients following radiation
treatment and chemotherapy.
• CEA may also be elevated in patients with liver damage
due to prolonged clearance.
• The upper normal range for serum CEA is 3 to 5 ng/mL
depending on the assay.

22. Frequently ordered Tumor markers
• The main clinical use of CEA is as a marker for
colorectal cancer.
• In colon cancer, CEA is used for prognosis, in
postsurgery surveillance, and to monitor response to
chemotherapy.
• Human chorionic gonadotropin (hCG) : is hormone
normally secreted by trophoblasts to promote
implantation of the blastocyst and the placenta to
maintain the corpus luteum through the first trimester of
pregnancy.
• hCG is elevated in trophoblastic tumors, mainly
choriocarcinoma, and germ cell tumors of the ovary and
testis.

23. Frequently ordered Tumor markers
• hCG has several clinical applications as a tumor marker.
• It is a prognostic indicator for ovarian cancer, a diagnostic
marker for classification of testicular cancer, and the most
useful marker for detection of gestational trophoblastic
diseases (GTDs)
• In testicular cancer, the free β-hCG subunit is elevated in
60% to 70% of patients with nonseminomas.
• hCG can be used in combination with AFP and biopsies to
diagnose subtypes of testicular cancer.
• Ectopic β-hCG is also occasionally elevated in ovarian
cancer and some lung cancers. In practice, free β-hCG is
sensitive and specific for aggressive neoplasms; the free β-
hCG is not detectable in the serum of healthy subjects.

24. Frequently ordered Tumor markers
• Postrate-specific antigen (PSA): PSA is a 28-kD
glycoprotein produced in the epithelial cells of the acini
and ducts of the prostatic ducts in the prostate.
• It is a serine protease of the kallikrein gene family.
• It functionally regulates seminal fluid viscosity and is
instrumental in dissolving the cervical mucus cap,
allowing sperm to enter.
• In healthy men, low circulating levels of PSA can be
detected in the serum.
• There are two major forms of PSA that are found
circulating in the blood: (1) free and (2) complexed.
• Most of the circulating PSA is complexed to α1-
antichymotrypsin or α2-macroglobulin.

25. Frequently ordered Tumor markers
• Assays to detect total and free PSA have been developed.
• The detection of total PSA has been used in screening for
and in monitoring of prostate cancer.
• As with other tumor markers, PSA is not entirely
specific.
• Men with benign prostatic hyperplasia (BPH) and
prostatitis can also have high PSA levels.
• Standard cutoff values of total PSA <4 ng/mL is
generally considered normal.
• PSA is measured by immunoassay, which detects both
free PSA and PSA complexed with α1-antichymotrypsin
but not α2-macroglobulin.
• Most immunoassays commercially available use
enzyme, fluorescence, or chemiluminescence on an
automated immunoassay platform