[609] Detection of Human Papillomavirus in Small Cell Carcinomas the Anus and Rectum.

Ashley Cimino-Mathews, Rajni Sharma, Peter B Illei. Johns Hopkins Medical Institutions, Baltimore, MD

Background: Anorectal squamous cell carcinomas are often associated with high-risk human papillomavirus infection, whereas most rectal cancers are adenocarcinomas that are not. Small cell carcinomas represent less than 1% of all colorectal/anlal carcinomas and have a poor prognosis. In the uterine cervix, small cell carcinomas are associated with HPV infection. HPV is usually detected by in situ hybridization or other nucleic acid based molecular techniques (i.e. polymerase chain reaction). In HPV infection the oncoprotein E7 inctivates the tumor suppressor Rb leading to upgregulation of p16. In small cell carcinomas, the Rb pathway is often blocked by other mechanisms thus the increased levels of p16 may not be indicative of HPV infection and therefore p16 immunohistochemistry has a limited role.
Design: We have identified 17 cases of anal/rectal small cell carcinomas in our files. Formalin-fixed, paraffin-embedded tissue from small cell carcinomas of the anus (n = 6) and rectum (n = 11) from 17 patients were subjected to immunohistochemistry for p16, CDX2 and p63, followed by in situ hybridization for high risk HPV types using the HPV Inform III family 16 kit (Ventana Medical Sytems, Tucson, AZ) and an HPV-16 genotype specific probe (Dako, Carpintera, CA). At the time of original diagnosis all 17 cases had at least one positive neuroendocrine marker (synaptophysin, chromograninn or CD56) described.
Results:

Number and percent of cases positive according to site
 AnusRectum
p16 IHC6/6 (100%)11/11 (100%)
HPV in situ4/5 (80%)7/9 (78%)
CDX-2 IHC1/6 (17%)5/9 (55%)
p63 IHC5/6 (83%)6/9 (67%)
IHC: immunohistochemistry

Two cases showed high viral copies, while the majority of cases showed low or very low HPV copy numbers. In 5 cases HPV could only be detected using the HPV-16 genotype specific assay that can detect 1-2 copies of HPV. A tumor was considered CDX-2 or p63 positive if at least 50% of the nuclei were positive irrespective of staining intensity. All but one anal tumor showed weaker p63 staining than the strong nuclear staining observed in the nuclei of anal squamous epithelium. The majority of CDX-2 positive tumors showed diffuse staining.
Conclusions: High risk type HPV can be detected using in situ hybridization in the majority of anorectal small cell carcinomas that are uniformly p16 positive by immunohistochemistry. The majority of tumors also express p63, which is more pronounced in the anal tumors. CDX-2 expression is also observed, predominntly in rectal tumors. HPV targeted therapy could result in better control of these aggressive neopalsms.
Category: Gastrointestinal

Wednesday, March 2, 2011 9:30 AM

Poster Session V # 36, Wednesday Morning

 

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