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.
|p16 IHC||6/6 (100%)||11/11 (100%)|
|HPV in situ||4/5 (80%)||7/9 (78%)|
|CDX-2 IHC||1/6 (17%)||5/9 (55%)|
|p63 IHC||5/6 (83%)||6/9 (67%)|