Abstract P2-06-15: The Use of ADH-5 Stain as a Surrogate Marker for Molecular Classification of Basal and Luminal Breast Cancers

Abstract

Abstract BACKGROUND: Immunohistochemical (IHC) analyses of protein expression have recently been used as surrogate assays for the molecular classification of breast cancers. Specifically, ER+/PR+/HER2- tumors are typically considered luminal-type breast cancers, ER-/PR-/HER2+ tumors equate to HER2 over-expressing tumors, whereas ER-/PR-/HER2- (triple negative, TN) tumors are basal-like breast cancers. A newly available cocktail of antibodies called ADH-5 allows for the simultaneous evaluation of both luminal and basal keratins. In this study, we examine the expression of luminal and basal keratins in breast cancers stained with ADH-5, particularly in a subgroup of basal keratin positive tumors. METHODS: All invasive breast cancers from 12/2009-6/2010 in a single pathology laboratory were studied by ADH-5 antibody cocktail consisting of two luminal keratin (LK) markers (CK7 and CK18), and two basal keratin (BK) markers (CK5 and CK14), as well as a myoepithelial marker, P63 (Biocare, Concord, CA). ER, PR, HER2 and Ki-67 were also evaluated by IHC and scored in all tumors. The group included 81 breast cancers and 3 metastatic tumors from the breast. ADH-5 staining was evaluated in areas of invasive carcinoma, and intensity and proportion of staining by BK and LK were scored. Mean statistics and ratios were evaluated and compared for each of the scored stains using the student t-test (stt) and chi squared analysis (cs), respectively. RESULTS: Of the 84 cancers, 20 (24%) showed some staining for BK, and 63 (75%) showed only LK staining. One case (1%) showed no staining for either BK or LK. Of the BK+ cases, 19/20 (95%) showed some degree of LK staining as well. Only one BK+ tumor lacked luminal keratin positivity (5%). Co-expression both BK and LK was seen in the same cells, though many cells were more strongly positive for one keratin type. The BK+ tumors were significantly more likely to be TN (p = 0.5, cs), and all TN tumors showed some BK staining. Four ER+/PR+/HER2- tumors expressed low levels of BK; two additional ER+/PR+/HER2+ tumors also expressed BK. ER-, PR-and TN tumors tended to show a significantly greater proportion of BK staining and decreased amount of luminal staining than ER+, PR+ and non-TN tumors. DISCUSSION: ADH-5 stain demonstrates co-expression of luminal keratins in basal keratin positive breast cancers, including all triple negative breast cancers in our study. In addition, some ER+/PR+/HER2- tumors and ER+/PR+/HER2+ (considered luminal A and B, respectively, by current usage of ER/PR/HER2 as surrogate markers) actually express basal keratins, bringing up the issue of whether these tumors should be considered luminal or basal-like. The ADH-5 stain may be helpful as a surrogate molecular marker for the classification of breast cancers. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-15.