Comparative and Additive Sensitivities of Immunohistochemical Markers of Breast Cancer Using New Monoclonal Antibodies to GCDFP-15 and Mammaglobin
AJ Shaw, LC Goldstein, PL Kandalaft, HC Hwang, SJ Kussick, AM Gown. PhenoPath Laboratories, Seattle, WA; IMPRIS, Seattle, WA
Background: Gross cystic disease fluid protein-15 (GCDFP-15) is a glycoprotein expressed by apocrine cells and in primary breast carcinomas. Mammaglobin is expressed almost exclusively in mammary epithelium, and is also a specific marker for breast carcinoma. Previous studies have shown that the sensitivities of GCDFP-15 and mammaglobin in breast carcinomas are both around 50% with a significant increase in sensitivity when combined (70%). Expression of both proteins has been used to identify breast carcinoma in the context of carcinoma of unknown origin. We wished to test the sensitivity of a new mouse monoclonal antibody (MoAb) to GCDFP-15 and compare its sensitivity to mammaglobin for the detection of breast carcinomas.
Design: A series of 322 breast carcinomas were tested on whole tissue sections for expression of GCDFP-15 and mammaglobin by immunohistochemistry (IHC) using the mouse MoAb to GCDFP-15 (Novocastra, clone 23A3) and a rabbit MoAb to mammaglobin (Zeta, Corp, clone 31A5). Antibody detection was by EnVision Plus polymer IHC (DAKO, Carpinteria, CA.) Scoring was based on percentage of positive tumor cells: negative (0%), rare cells (<1%), focal (1-25%), variable (26-75%), uniform (>75%).
Results: The overall sensitivity of the MoAb antibody to GCDFP-15 was 80.4%, compared with 59.9% for mammaglobin; 13.3% of breast cancers were negative with both antibodies, yielding a combined sensitivity of 86.7%. The number of cases that were GCDFP-15 positive/mammaglobin negative was 86/322 (26.7%) and GCDFP-15 negative/mammaglobin positive was 20/322 (6.2%.) Many of the cases showed heterogeneous staining for GCDFP-15 with 44/322 (13.7%) cases with only rare cells positive.
Conclusions: Clone 23A3, a new monoclonal antibody to GCDFP-15 demonstrated considerably higher sensitivity (80.4%) compared with the 50% sensitivity historically reported for earlier generation anti-GCDFP-15 antibodies for the detection of breast carcinomas. There was a small subset of cases (6.2%) that showed expression of mammaglobin but were negative for GCDFP-15. Evaluation of these two antigens together may maximize the ability to identify breast carcinoma when tumor origin is unknown. The expression of GCDFP-15 was heterogeneous in many tumors, with 13.7% showing only rare cells positive (<1%.) Therefore the increase in sensitivity seen in this report may not be replicable in tissue microarray-based studies.
Tuesday, March 10, 2009 9:15 AM
Platform Session: Section B, Tuesday Morning