[306] Mesothelin, a Targetable Surface Protein, Is Highly Expressed in Breast Carcinomas in African American Women

Rena Xian, Tchou Julia, Ziober Amy, Robert Vonderheide, Carl June, Zhang Paul. Hospital of the University of Pennsylvania, Philadelphia, PA

Background: Even when adjusted for cancer stage and treatment, African American (AA) women with breast cancer (BRCA) have worse prognosis than non-AA women. Recent studies have shown that AA women are also more likely to have triple negative breast cancers (TNBC), a poor prognosis BRCA subtype that lacks targeted therapy. We have previously demonstrated that mesothelin, a cell surface glycoprotein, is preferentially expressed in TNBC, as compared to ER/PR+ and HER2+ BRCA. Since AA women are likely to have TNBC, we set out to evaluate the disparity, if any, of mesothelin expression in BRCA derived from AA and Caucasian (CC) women, as anti-mesothelin therapy may be an effective strategy in decreasing the cancer burden in AA women.
Design: Expression of Mesothelin was evaluated in 118 patients with BRCA - 65 TNBC (26 CC, 39 AA), 24 ER+/HER2- (18 CC, 6 AA), and 29 HER2+ (21 CC, 8 AA). We used an anti-mesothelin antibody (5B2, NeoMarker, 1:20) by standard immunohistochemical methods on paraffin sections of the above cases retrieved from our institutional files from 2009-2011. Positive staining was scored as a product of staining extent (%) and intensity (1+, 2+, 3+) with a maximal score of 300. A score of 5 or greater was considered positive.
Results: Mesothelin is expressed in 44% of all BRCA cases with this breakdown: 75% of TNBCs, 0% of ER+/HER2- (p=0.0004), and 10% of HER2+ (p=0.0018) BRCA. No mesothelin reactivity is noted in non-neoplastic mammary epithelium. When stratified by race, differences in mesothelin expression are found between AA and CC patients (see Table 1).

Table 1. Expression of mesothelin AA and CC patients (n=118).
 Mesothelin positivity in AA patients (% of cases/mean IHC staining score)Mesothelin positivity in CC patients (% of cases/mean IHC staining score)p-value
All Cases52/43.328/14.50.003
TNBC82/58.365/28.60.052
ER/PR+0/00/00.575
HER2+25/3.15/9.30.690



Conclusions: We report here that mesothelin is expressed in a significantly larger proportion of BRCA in AA women as compared with BRCA in CC. Our finding supports the hypothesis that AA women develop distinct BRCA given known differences in clinical presentation, treatment, and outcome. As novel cell based immunotherapy targeting mesothelin in mesothelioma, and other mesothelin positive adenocarcinomas, is underway, our results suggest that AA patients may be more likely to be eligible for this novel therapy, which could potentially close the disparity gap in treatment outcomes.
Category: Breast

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 45, Monday Morning

 

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