title: Detection of human papillomavirus in small cell carcinomas of the anus and rectum.
abstract: Small cell carcinomas represent <1% of colorectal/anal carcinomas and have a poor prognosis. Anorectal squamous cell carcinomas are often associated with high-risk human papillomavirus (HPV) infection, similar to squamous and small cell carcinomas of the uterine cervix. In HPV infection, the oncoprotein E7 inactivates the tumor suppressor Rb, leading to p16 upregulation; however, in small cell carcinomas, the Rb pathway is often blocked by other mechanisms; thus, increased p16 may not indicate HPV infection. P16 immunohistochemistry (IHC) may have a limited role in evaluating small cell carcinomas for HPV infection. Formalin-fixed, paraffin-embedded tissue sections of previously diagnosed small cell carcinomas of the anus (n=5) and rectum (n=11) were subjected to IHC for p16, CDX2, and p63, followed by in situ hybridization for high-risk HPV. All (100%) cases of anal and rectal small cell carcinomas were positive for p16, and 100% of anal and 82% of rectal small cell carcinomas were positive for high-risk HPV. The majority of cases showed low or very low HPV copy numbers. In 6 cases, HPV was detected only by using the HPV-16 genotype-specific assay detecting very low copy numbers (1 to 2 viral copies). The majority of tumors expressed p63, which was more pronounced in the anal tumors. CDX2 expression was observed predominantly in rectal tumors. High-risk HPV can be detected using in situ hybridization in the majority of anorectal small cell carcinomas, which are uniformly p16 positive by IHC. HPV-targeted therapy could result in better control of these aggressive neoplasms.
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21231, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Cimino-Mathews
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.forename: Peter B
authors.initials: PB
authors.lastname: Illei
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000821:virology*; D015142:Baltimore; D014408:Biomarkers, Tumor / Q000032:analysis; D000071616:CDX2 Transcription Factor; D018288:Carcinoma, Small Cell / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D004279:DNA, Viral / Q000302:isolation & purification*; D005260:Female; D005404:Fixatives; D005557:Formaldehyde; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000401:mortality / Q000821:virology*; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D012004:Rectal Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000821:virology*; D016019:Survival Analysis; D016707:Tissue Fixation / Q000379:methods; D014157:Transcription Factors / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D005404:Fixatives; D018398:Homeodomain Proteins; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D005557:Formaldehyde