CK 17 marker in identify AIN VS anal SCCA

1. KUSUMA CHINAROONCHAI
25 Feb 2014

2. BACKGROUND
Anal squamous cell carcinoma is rare
Risk is HPV infection >> anal intraepithelial neoplasia (AIN)
Problem in diagnosis of small tissue biopsy specimen and anal
gland involvement (AIN vs invasive)
Cytokeratin17 (CK17)is a basal/myoepithelial cell keratin induced
in activated keratinocytes and associated with disease
progression in SCC of uterine, cervix, esophagus, and oral cavity.

3. MATERIAL & METHODS
Cases 2009-2012 diagnosis of anal SCC, basaloid
SCC(BSCC) ,pure basaloid carcinoma and AIN
Files of the James Homer Wright Pathology Laboratories of the
Massachusetts General Hospital, Boston, MA and of Brighamand
Women’s Hospital, Boston, MA

4. MATERIAL & METHODS
BSCC: SCC with keratinization and basaloid features (ie,
peripheral palisading, smalls cell without distinct intercellular
bridges, and retraction artifact)
Pure BSCC: a tumour with basaloid features lacking
keratinzination or other features typical of SCC with
morphologic likeness to cutaneous basal cell carcinomas)
HPV status from in situ hybridization, polymerase chain reaction
testing, p16INK4a immunohistochemistry and previous reports

5. IMMUNOHISTOCHEMISTRY
5 mm thick sections of formalin-fixed paraffin-embedded tissue
primary antibodies against CK17 (cloneE3, 1:50, Dako,
Carpinteria, CA)
Studies staining
Negative VS positive
Pattern of staining expression

6. IMMUNOHISTOCHEMISTRY
Positive staining
Peripheral/rim (basal or outer 1/3)
Diffuse (basal and Up)
Negative staining
Absence
Surface/center (suprabasal or inner 2/3)
< 10% of basal cells

7. STATISTICAL ANALYSIS
Sensitivity
Specificity
Positive predictive value (PPV)
Negative predictive value (NPV)
Fisher’s exact test
Significant P-value < 0.05

8. RESULTS
33 cases from 27 patients
12 typical SCCs (2 papillary architecture)
8 invasive BSCCs
2 invasive pure BSCCs
11 AIN
6 patients (5 SCCs + 1 BSCC) concurrent with AIN

10. RESULTS
24 (92%) HPV positive
100% (20/20) of invasive SCCs and BSCCs >> +ve CK17 stain
92% (11/12) in invasive SCCs >> diffuse staining (1/12 peripheral
staining)
75% (6/8) in BSCCs >> diffuse staining (2/8 peripheral staining)

11. RESULTS
Diffuse positive CK 17 in each histologic pattern
83% (10/12) Infiltrative pattern of invasion in SCCs and BSCCs
86% (7/8) Blunt-type invasion
2 pure BSCCs negative for CK17, positive for p16

12. RESULTS
45% (5/11) AIN surface CK17 staining (Grade3/high grade dysplasia)
1/11 AIN focal peripheral staining in worrisome area of invasion in H&E
stain
5/11 AIN negative CK17
6 invasive + AIN
5 diffuse CK17 in invasive lesion
1 Positive CK17 in both AIN and invasive lesion

13. SCCS & DIFFUSE CK17

14. BSCCS & DIFFUSE CK17

15. PURE BSCCS & -VE CK17 & P16

16. AIN 3 & SURFACE CK17

17. AIN 3 & DIFFUSE CK17

18. AIN 3 WITH SUSPECTED EARLY
INVASION & BASAL CK17

19. SCCS + AIN 3 & CK17 PATTERN

20. NORMAL SQUAMOUS
EPITHELIUM & CK17

21. RESULTS

22. DISCUSSIONS
AIN 1 or low grade dysplasia: lower 1/3 epithelium >> topical
agents treatment as imiquimod
AIN 2 or 3 or high grade dysplasia: 2/3 or all epithelium >>
excision

23. DISCUSSIONS
Problem in anal biopsy specimen
Presence vs absence AIN
Degree of dysplasia
***Presence vs absence invasive carcinoma***
Small pieces and poorly oriented
Cell extended to anal gland
Inflammation cell infiltrate

24. DISCUSSIONS
Insitu lesion >> local excision
Invasive lesion >> excision plus CMT & RT
Previous studies report increased expression of CK17 in SCCs
when compared with normal adjacent tissue in cervix, oral cavity,
larynx, esophagus and lung. (Ikeda et al, Kitamura et al, Purkis et
al and Chu and Weiss.)

25. DISCUSSIONS
Williams et al showed that CK17 is expressed in basal cells of
the normal epithelium of the distal anal canal and perianal skin,
but in our laboratory CK17 staining was not seen in the normal
squamous epithelium of the anal canal or perianal skin.
A potential pitfall in the utility of CK17 is that the rare pure
basaloid variant of anal carcinoma is negative for CK17.
P16 positive in the rare pure basaloid variant of anal carcinoma
may reflect pathogenesis process.

26. “THANK YOU.”
FOR YOUR ATTENTION