Carbonic Anhydrase IX, p16 and Human Papillomavirus Infection in Endocervical Glandular Neoplasia Associated with Lobular Endocervical Glandular Hyperplasia: A Gynecologic Oncology Group Study
SY Liao, WH Rodgers, J Kauderer, KM Darcy, R Carter, L Levine, NM Spirtos, N Susumu, K Fujiwara, JL Walker, M Hatae, EJ Stanbridge. UC Irvine, Irvine; Lenox Hill Hosp., NY; GOG Statistical and Data Center, Buffalo; Univ. of Taxas, Galveston; Univ. of Nevada School of Medicine, Las Vegas; Keio Univ. School of Medicine, Keio, Japan; Saitama Medical Univ. Int. Medical Center, Hidaka City, Japan; Univ. of Oklahoma, Oklahoma; Kagoshima City Hosp., Kagoshima, Japan
Background: Lobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. Others propose that LEGH represents pre-cancerous minimal deviation adenocarcinoma (MDA) independent of high-risk human papillomavirus (H-HPV) infection. Carbonic anhydrase IX (CAIX), a hypoxic marker, is highly expressed in neoplastic cervical glandular lesions (GLs), including in-situ and invasive adenocarcinoma. Expression of CAIX in LEGH and MDA has not been reported. We report a comparative study of CAIX, p16 expression and H-HPV infection in conventional GLs (CGLs) and LEGH.
Design: In 1998, the Gynecologic Oncology Group initiated an international trial to evaluate the diagnostic utility of CAIX expression and H-HPV in women with a cytologic diagnosis of atypical glandular cells from the United States (U.S.) and Japan. Pathological diagnoses were based on diagnostic criteria for LEGH proposed by Nucci et al. Immunostaining was used to detect CAIX and p16. Polymerase chain reaction was used to detect H-HPV in liquid based cytology specimens.
Results: No cases of LEGH were observed in the U.S. cohort. In the Japanese cohort, we identified 15 CGLs and 14 LEGHs (six had coexistent well-differentiated GLs and all but one had variable cytologic atypia). HPV testing was performed on 13 of 15 CGLs and 11 (85%) were infected with H-HPV. All of the HPV positive CGLs showed high levels of CAIX and p16 expression with the exception of one. The one p16 negative CGL was also negative for H-HPV. Among the 14 LEGH lesions, none of them were infected with H-HPV and all expressed CAIX. They were either negative for p16 expression or showed low levels of p16 expression.
Conclusions: The results support different mechanisms of carcinogenesis in conventional GLs verses GLs associated with LEGH. CAIX expression may serve as a specific marker for detection of LEGH in the absence of H-HPV.
Category: Gynecologic & Obstetrics
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 180, Tuesday Morning