Mesothelin Expression in Triple Negative Breast Carcinomas Correlates Significantly with Basal-Like Phenotype, Distant Metastases and Decreased Survival
Gary Tozbikian, Edi Brogi, Kyuichi Kadota, Jeffrey Catalano, Akram Muzaffar, Sujata Patil, Prasad S Adusumilli, Larry Norton, Yong H Wen. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Mesothelin (MES) is an antigen expressed in some human malignancies. Immunotherapies targeting MES are being developed. The clinicopathologic and prognostic significance of MES expression in triple negative breast carcinomas (TNs) has not been fully assessed.
Design: We evaluated the expression of MES (clone 5B2, Vector Laboratories) and basal markers (CK5/6, CK14, EGFR) in tissue microarrays of 226 TNs and 88 non-TNs. We scored percentage (score 0=0%, 1=1-50%, 2=51-100%) and intensity (score 0=no signal, 1=weak, 2=moderate, 3=strong) of MES staining in tumor cells and regarded cases with sum score >3 as positive (MES(+)). Statistical analysis used t-test to correlate MES(+) with basal phenotype and clinicopathologic features, and Kaplan-Meier method (KM) and log-rank test to evaluate overall survival (OS) and disease-free survival (DFS) based on MSLN positivity, basal-like phenotype and lymph node (LN) status.
Results: Patients (pts) with TNs and non-TNs had similar age (mean 56 +14 vs 54 +15 years (y)). Significantly more TNs than non-TNs were MES(+) (82/226, 36% vs 14/88, 16%; p= 0.0006). In TNs, MES reactivity significantly correlated with CK5/6 (56/80, 70%; p= <0.00001) and CK14 (29/72, 40%; p=0.017), but not with EGFR (57/78, 73%; p=0.87). Histologic grade (p=0.49) and subtype (p=0.29), median size (2.3 cm+ 2.9 vs 2.5 cm+ 2.4; p=0.70), lymphovascular invasion (44% vs 33%; p=0.11), and LN metastases (50% vs 42%; p=0.26) did not differ in MES(+)TNs vs MES(-)TNs. Pts with MES(+)TN were older than pts with MES(-)TN (58+14 vs 54+14 y; p=0.04), had significantly lower OS and DFS than pts with MES(-)TN. They developed more distant metastases (16/69, 23% vs 12/126, 9.5%) with shorter interval (19+11 vs 35+18 months). Significance persisted in log-rank tests of basal-like phenotype and LN status. [Table 1]
|MES(-) TN, n=144||MES(+) TN, n=82||p value|
|OS||0.91 (0.83-0.95)||0.66 (0.52-0.77)||0.0001|
|DFS||0.86 (0.79-0.92)||0.67 (0.54-0.77)||0.0003|
|Basal keratin(+)||0.92 (0.80-0.97)||0.62 (0.45-0.75)||0.0002|
|Basal keratin(-)||0.90 (0.78-0.96)||0.90 (0.47-0.98)|
|LN(+)||0.87 (0.70-0.94)||0.57 (0.35-0.73)||0.0003|
|LN(-)||0.94 (0.85-0.98)||0.76 (0.57-0.87)|