An Immunohistochemical Panel Comprised of HNF-1β, WT-1, and PAX 2 To Distinguish Ovarian Clear Cell Carcinomas from Ovarian Serous Carcinomas and Metastatic Renal Clear Cell Carcinomas.
Molly E Klein, David J Dabbs, Gloria J Carter, Mamatha Chivukula. Magee-Womens Hospital of UPMC, Pittsburgh, PA
Background: Ovarian clear cell carcinomas (OCCC) are uncommon ovarian epithelial tumors with unique clinical behavior, including poor response to platinum-based chemotherapy. Although OCCC often display characteristic morphologic features, there can be considerable overlap with other ovarian epithelial tumors (most often, ovarian serous carcinoma (OSC)) and with metastatic tumors such as renal clear cell carcinoma (RCCC). We studied the pattern of expression of three markers by OCCC, OSC and RCC. In addition to Wilm's tumor 1 protein (WT-1, a mesothelial marker expressed in OSC but uncommonly expressed in OCCC), the immunohistochemical panel includes Hepatocyte Nuclear Factor-1β (HNF-1β) and PAX 2. HNF-1β is expressed in renal tubules and collecting ducts but is not significantly expressed in adult ovaries or testes. It is aberrantly expressed in OCCC, but is rarely expressed in other ovarian epithelial tumors. PAX 2 is expressed in normal endometrium and tubal epithelium. Prior studies have shown its expression in mullerian tumors such as OSC, and have described it as a marker of mullerian origin in metastatic tumors. The aim of our study is to describe the expression of these three markers in OCCC, OSC and RCCC, to facilitate the use of this panel to aid in the diagnosis of morphologically challenging cases.
Design: Cases of OCCC (33), OSC (10) and RCCC (6) were retrieved by searching our pathology database. Immunohistochemical stains were performed on formalin fixed paraffin embedded tissue using three antibodies: rabbit polyclonal HNF-1β (Sigma Prestige), rabbit polyclonal PAX 2 (Invitrogen-Zymed Laboratories) and WT-1 (clone 6F-H2, Ventana Medical). We assigned an intensity score (IS) of 0 (negative), 1 (weak), 2 (moderate) or 3 (strong), and a proportion score of 0 (0 to <1%), 1 (≥1 to 5%), 2 (6 to 20%), 3 (21% to 80%) or 4 (>80%). The cumulative score (CS) is the sum of the IS and PS.