title: Comparative analysis of Napsin A, alpha-methylacyl-coenzyme A racemase (AMACR, P504S), and hepatocyte nuclear factor 1 beta as diagnostic markers of ovarian clear cell carcinoma: an immunohistochemical study of 279 ovarian tumours.
abstract: Napsin A and α-methylacyl-coenzyme A racemase (AMACR, P504S) have recently been described as being frequently expressed in clear cell carcinomas (CCC) of the gynecological tract. The present study was conducted to assess the test performance of these newer markers relative to the more traditional marker, hepatocyte nuclear factor 1β (HNF1β), in a large and histotypically diverse dataset. A total of 279 ovarian tumours in tissue microarrays were immunohistochemically assessed for the expression of Napsin A, AMACR and HNF1β. HNF1β, Napsin A and AMACR were expressed in 92%, 82% and 63% of 65 CCC, 7%, 1% and 1% of 101 serous carcinomas, 37%, 5.3% and 0% of 19 endometrioid carcinomas, 60%, 0% and 0% of 45 mucinous tumours, 100%, 0% and 0% of seven yolk sac tumours, and 0%, 16.7% and 16.7% of six steroid cell tumours NOS, respectively. All other tumours, including 18 adult-type granulosa cell tumours, eight dysgerminomas and nine other miscellaneous tumour types were negative for all three markers. Using a benchmark of ≥1% of tumour cells for positivity and CCC as the diagnostic end-point, the sensitivity, specificity, negative predictive value and positive predictive value of Napsin A expression were 0.82, 0.99, 0.94, and 0.98, respectively (odds ratio 439, p < 0.0001). Respective parameters were 0.92, 0.79, 0.97, and 0.58 (odds ratio 44, p < 0.0001) for HNF1β and 0.63, 0.99, 0.89, and 0.5 (odds ratio 112, p < 0.0001) for AMACR. The combination of any two positive markers, irrespective of the staining pattern of the third, significantly predicted the CCC histotype in every analytic scenario. In summary, HNF1β is highly sensitive but is suboptimally specific in isolation, whereas AMACR is highly specific but is suboptimally sensitive. Napsin A is specific but of intermediate sensitivity. Napsin A, AMACR and HNF1β are all viable markers of CCC that can be deployed as components of larger panels when CCC is a diagnostic consideration.
authors.affiliation: 1Department of Pathology, University of California San Diego, San Diego, CA 2Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA 3Departments of Obstetrics and Gynecology, and of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 4Department of Pathology, Yale University School of Medicine, New Haven, CT 5Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 6Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 7Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Oluwole
authors.initials: O
authors.lastname: Fadare
authors.forename: Chengquan
authors.initials: C
authors.lastname: Zhao
authors.forename: Dineo
authors.initials: D
authors.lastname: Khabele
authors.forename: Vinita
authors.initials: V
authors.lastname: Parkash
authors.forename: Charles M
authors.initials: CM
authors.lastname: Quick
authors.forename: Katja
authors.initials: K
authors.lastname: Gwin
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Desouki
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D051539:Hepatocyte Nuclear Factor 1-beta / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D019998:Racemases and Epimerases / Q000378:metabolism*; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D051539:Hepatocyte Nuclear Factor 1-beta; D016282:Aspartic Acid Endopeptidases; C498549:NAPSA protein, human; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase