title: Mesothelin expression in triple negative breast carcinomas correlates significantly with basal-like phenotype, distant metastases and decreased survival.
abstract: Mesothelin is a cell surface associated antigen expressed on mesothelial cells and in some malignant neoplasms. Mesothelin-targeted therapies are in phase I/II clinical trials. The clinicopathologic and prognostic significance of mesothelin expression in triple negative breast carcinomas (TNBC) has not been fully assessed. We evaluated the expression of mesothelin and of basal markers in tissue microarrays of 226 TNBC and 88 non-TNBC and assessed the clinicopathologic features of mesothelin-expressing breast carcinomas. Furthermore, we investigated the impact of mesothelin expression on the disease-free and overall survival of patients with TNBC. We found that mesothelin expression is significantly more frequent in TNBC than in non-TNBC (36% vs 16%, respectively; p = 0.0006), and is significantly correlated with immunoreactivity for basal keratins, but not for EGFR. Mesothelin-positive and mesothelin-negative TNBC were not significantly different by patients' race, tumor size, histologic grade, tumor subtype, lymphovascular invasion and lymph node metastases. Patients with mesothelin-positive TNBC were older than patients with mesothelin-negative TNBC, developed more distant metastases with a shorter interval, and had significantly lower overall and disease-free survival. Based on our results, patients with mesothelin-positive TNBC could benefit from mesothelin-targeted therapies.
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Gary
authors.initials: G
authors.lastname: Tozbikian
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Edi
authors.initials: E
authors.lastname: Brogi
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Kadota
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Catalano
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Akram
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Sujata
authors.initials: S
authors.lastname: Patil
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Alice Y
authors.initials: AY
authors.lastname: Ho
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Britta
authors.initials: B
authors.lastname: Weigelt
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Prasad S
authors.initials: PS
authors.lastname: Adusumilli
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Hannah Yong
authors.initials: HY
authors.lastname: Wen
mesh_terms: D001940:Breast / Q000473:pathology*; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis*; D006801:Humans; D000090204:Mesothelin; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis / Q000473:pathology*
chemical_list: D058851:GPI-Linked Proteins; D000090204:Mesothelin