HPV Is Associated with Many Types of Rare Cervical Cancer
SM Tucker, JA Hanson, V Rajendran, Z Peng, CS-C Adamson, K Cooper, MF Evans. Fletcher Allen Health Care, Burlington, VT; University of Vermont, Burlington, VT
Background: The role of human papillomaviruses (HPV) in the pathogenesis of squamous cell carcinoma (SCC) of the cervix is well-established. However, the significance of HPV in the etiology of rare cervical cancer types is largely unknown; the aim of this study was to investigate HPV in these tumors by combining polymerase chain reaction (PCR), chromogenic in situ hybridization (CISH) and immunohistochemical (IHC) assays.
Design: Thirty-one archival (1995-2008) formalin-fixed, paraffin-embedded samples of adenoid basal carcinoma (AB, n=6), adenoid cystic carcinoma (AC, n=4), adenosquamous carcinoma (AS, n=9), basaloid squamous carcinoma (BS, n=1), mesonephric adenocarcinoma (MA, n=1), mucinous adenocarcinoma (MuA, n=7), small cell carcinoma (SC, n=2), and transitional cell carcinoma (TC, n=1) were collected from 23 patients. PCR was performed using GP5+/6+ primers, CISH using biotinyl-tyramide amplification, and IHC for p16INK4a.
Results: HPV was detectable by PCR in all types of rare cervical tumors. High-risk (hr) types (HPV16 [n=8], 18 [n=6], 31 [n=3], 33 [n=2], 45 [n=1], 59 [n=4], 66 [n=1]) low-risk (lr) types (HPV11 [n=1]) and an unidentified type or types [n=1] were detected. Four individual samples were PCR negative for HPV (2 AC, 2 MuA). CISH signals (punctate [integrated HPV] or both punctate and diffuse [integrated and episomal HPV]) were detected in 1/2 AC, 6/9 AS, 1/1 BS, 1/2 SC and 1/1 TC samples. CISH signals were not detected in any of the AB or MuA samples. p16INK4a staining demonstrated no identifiable pattern for any tumor type. p16INK4a staining was identified in samples that were negative for HPV by PCR/CISH and was absent in PCR positive samples; all CISH positive samples demonstrated some p16INK4a staining.
Conclusions: This study is the first to combine PCR, CISH and p16INK4a IHC in the investigation of the role of HPV in rare types of cervical cancer. The data indicate that HPV is associated with at least a subset of adenoid cystic, adenosquamous, basaloid squamous, small cell and transitional cell carcinomas and for a broad range of hrHPV types. The non-detection of HPV by CISH in PCR positive adenoid basal carcinomas and mucinous adenocarcinomas allows for the possibility that in these tumors the HPV detected is incidental to tumor pathogenesis. p16INK4a staining does not appear to be a surrogate marker for HPV across the variety of rare cervical tumor forms.
Category: Gynecologic & Obstetrics
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 165, Monday Morning