Identification of an Effective Immunohistochemical Panel in Distinction of Breast Carcinoma from Ovarian Serous Carcinoma
Fan Lin, Jeffrey Prichard, Mary (Xiaohong) Zhang, Haiyan Liu. Geisinger Medical Center, Danville, PA
Background: When working on a tumor of unknown origin, breast carcinoma (BCA) versus ovarian serous carcinoma (OSCA) may present a diagnostic challenge because of the overlapping morphological features and immunostaining profile. In this study, we re-evaluate the expression of an extensive panel of biomarkers including recently described markers GATA3, Trefoil factor 1 (TFF1) and Trefoil factor 3 (TFF3) using a single immunostaining system (Dako).
Design: We immunohistochemically evaluated the expression of 1) epithelial markers (AE1/3, CAM5.2, CK7, CK20, CK17, CK19, CK903, EMA); 2) mucin gene products (MUC1, MUC2, MUC4, MUC5AC, MUC6); 3) tumor suppressor genes and transcription factors (ER, PR, p53, beta-catenin, WT-1, CDX2, pVHL); and 4) tumor-associated proteins (TTF-1, napsin A, GATA3 [Santa Cruz; sc-268], TFF1 [Epitomics; AC0045], TFF3 [Epitomics; AC0103], FOXA1, ERG, HepPar1, glypican 3, SALL4, OCT4, PAX2, PAX8, RCC GCDFP-15, mammaglobin, S100P, IMP3, maspin, MOC31, CEA, CA19-9, CA125, CD10, CD15, villin, and P504S) on 146 cases of breast carcinoma (98 ductal carcinomas and 48 lobular carcinomas) and 41 cases of ovarian serous carcinoma on tissue microarray sections. The staining intensity was graded as weak or strong. The distribution was recorded as negative (<5% of tumor cells stained), 1+ (5-25%), 2+ (26-50%), 3+ (51-75%), or 4+ (>75%).
Results: The positive staining results from selected antibodies, which demonstrated diagnostic value, are summarized in Table 1. When combining ductal and lobular carcinomas, the positive staining results for GTAT3, TFF1 and TFF3 were 95%, 77%, and 88%, respectively, with a strong and diffuse staining (3+ or 4+) in 131 cases (90%), 79 cases (56%) and 103 cases (72%), respectively. For ovarian serous carcinomas, 38 cases (93%) %) were strongly and diffusely (3+ or 4+) positive for PAX 8, and 30 cases (73%) were strongly and diffusely (3+ or 4+) positive for WT-1.
|Antibody||Breast DCA||Breast LCA||OSCA|
|GATA3||90/98 (92%)||48/48 (100%)||0/41 (0)|
|TFF1||68/95 (72%)||41/47 (87%)||0/41 (0)|
|TFF3||81/96 (84%)||45/48 (94%)||3/41 (7%)|
|PAX8||0/98 (0)||0/48 (0)||41/41 (100%)|
|WT-1||0/98 (0)||0/48 (0)||36/41 (88%)|