Title | Carbonic anhydrase IX (CA-IX) and high-risk human papillomavirus (H-HPV) as diagnostic biomarkers of cervical dysplasia/neoplasia in Japanese women with a cytologic diagnosis of atypical glandular cells (AGC): a Gynecologic Oncology Group (GOG) Study. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Liao S-Y, Rodgers WH, Kauderer J, Bonfiglio TA, Darcy KM, Carter R, Levine L, Spirtos NM, Susumu N, Fujiwara K, Walker JL, Hatae M, Stanbridge EJ |
Journal | Br J Cancer |
Volume | 104 |
Issue | 2 |
Pagination | 353-60 |
Date Published | 2011 Jan 18 |
ISSN | 1532-1827 |
Keywords | Adult, Aged, Aged, 80 and over, Alphapapillomavirus, Carbonic Anhydrases, Female, Genotype, Humans, Japan, Middle Aged, Polymerase Chain Reaction, Uterine Cervical Dysplasia |
Abstract | BACKGROUND: High-risk human papillomavirus (H-HPV) infection is linked to cervical neoplasia but its role in detecting cervical glandular lesions (GLs) is unclear. Carbonic anhydrase IX (CA-IX) is a hypoxic biomarker that is highly expressed in neoplastic cervical GLs. The diagnostic utility of these biomarkers was evaluated by the Gynecologic Oncology Group in Japanese women with a cytological diagnosis of atypical glandular cells. METHODS: Immunostaining was used to detect CA-IX in a conventional Pap smear. Immunoreactivity of CA-IX was interpreted by a panel of pathologists blinded to the histological diagnosis. Polymerase chain reaction was used to detect H-HPV in a liquid-based cytology specimen. RESULTS: Significant cervical lesions (SCLs), defined as cervical intraepithelial neoplasia (CIN2, CIN3), adenocarcinoma in situ or invasive carcinoma, were observed in 37/88 (42%) of women. CA-IX testing alone (n=88) had a sensitivity of 89, 100 or 73% for SCLs, GLs or significant squamous lesions (SLs), respectively, with a false negative rate (FNR) of 14%. Testing for H-HPV (n=84) had a sensitivity of 65, 53 or 80% for SCLs, GLs or SLs, respectively, with a FNR of 22%. The combination of CA-IX and H-HPV testing had a sensitivity of 97, 100 or 93% for SCLs, GLs or SLs, respectively, with a FNR of 5%. Among eight H-HPV-negative GLs, six (75%) had a diagnosis of lobular endocervical glandular hyperplasia (LEGH). CONCLUSION: The combination of CA-IX and HPV testing improved the diagnostic accuracy. The low rate of H-HPV positivity in the GLs was associated with coexisting LEGH independent of H-HPV. |
DOI | 10.1038/sj.bjc.6606049 |
Alternate Journal | Br J Cancer |
PubMed ID | 21157448 |
PubMed Central ID | PMC3031897 |
Grant List | U10 CA037517 / CA / NCI NIH HHS / United States GOG38886 / / PHS HHS / United States CA 37517 / CA / NCI NIH HHS / United States CA 11479 / CA / NCI NIH HHS / United States CA 27469 / CA / NCI NIH HHS / United States U10 CA027469 / CA / NCI NIH HHS / United States |
Related Faculty:
William Rodgers, M.D., Ph.D.