Original study| Volume 13, ISSUE 5, P378-384, October 2013

Download started.


Mesothelin Expression and Survival Outcomes in Triple Receptor Negative Breast Cancer



      Mesothelin is an ideal tumor-associated marker for the development of targeted therapy due to its limited expression in normal tissues. The aim of this study was to evaluate mesothelin expression in triple-negative breast cancer (TNBC) and its correlation with survival outcomes.


      Mesothelin expression was completed by using immunohistochemistry and was quantified by the H score. An H score > 10 was considered positive. Patient characteristics were compared by mesothelin expression. The Kaplan-Meier product limit method was used to estimate survival outcomes. Cox proportional hazards models was used to adjust for patient and tumor characteristics.


      The median age was 52 years. Of the 109 patients with TNBC, 37 (34%) were positive for mesothelin expression. There were no differences on patient and/or tumor characteristics by mesothelin expression with the exception of high frequency of lymphovascular space invasion in mesothelin-negative tumors (2P = .03). At a median follow-up of 75.8 months, 20 (18.3%) patients had experienced a recurrence, and 22 (20.2%) had died. Five-year progression-free survival was 87% and 92% in patients with mesothelin-positive and those with mesothelin-negative tumors (2P = .43). Five-year overall survival was 85% and 91% in patients with mesothelin-positive and those with mesothelin-negative tumors (2P = .57), respectively. Mesothelin expression was not an independent predictor of survival outcomes.


      Mesothelin expression was identified in 34% of patients with TNBC. Mesothelin expression did not correlate with survival outcomes in patients with TNBC.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Breast Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Chang K.
        • Pastan I.
        Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers.
        Proc Natl Acad Sci USA. 1996; 93: 136-140
        • Bera T.K.
        • Pastan I.
        Mesothelin is not required for normal mouse development or reproduction.
        Mol Cell Biol. 2000; 20: 2902-2906
        • Rump A.
        • Morikawa Y.
        • Tanaka M.
        • et al.
        Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion.
        J Biol Chem. 2004; 279: 9190-9198
        • Chang K.
        • Pastan I.
        • Willingham M.C.
        Isolation and characterization of a monoclonal antibody, K1, reactive with ovarian cancers and normal mesothelium.
        Int J Cancer. 1992; 50: 373-381
        • Chang K.
        • Pai L.H.
        • Pass H.
        • et al.
        Monoclonal antibody K1 reacts with epithelial mesothelioma but not with lung adenocarcinoma.
        Am J Surg Pathol. 1992; 16: 259-268
        • Argani P.
        • Iacobuzio-Donahue C.
        • Ryu B.
        • et al.
        Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas: identification of a new pancreatic cancer marker by serial analysis of gene expression (SAGE).
        Clin Cancer Res. 2001; 7: 3862-3868
        • Swierczynski S.L.
        • Maitra A.
        • Abraham S.C.
        • et al.
        Analysis of novel tumor markers in pancreatic and biliary carcinomas using tissue microarrays.
        Hum Pathol. 2004; 35: 357-366
        • Hassan R.
        • Laszik Z.G.
        • Lerner M.
        • et al.
        Mesothelin is overexpressed in pancreaticobiliary adenocarcinomas but not in normal pancreas and chronic pancreatitis.
        Am J Clin Pathol. 2005; 124: 838-845
        • Hassan R.
        • Ho M.
        Mesothelin targeted cancer immunotherapy.
        Eur J Cancer. 2008; 44: 46-53
        • Cheng W.F.
        • Huang C.Y.
        • Chang M.C.
        • et al.
        High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma.
        Br J Cancer. 2009; 100: 1144-1153
        • Einama T.
        • Kamachi H.
        • Nishihara H.
        • et al.
        Co-expression of mesothelin and CA125 correlates with unfavourable patient outcome in pancreatic ductal adenocarcinoma.
        Pancreas. 2011; 40: 1276-1282
        • Baba K.
        • Ishigami S.
        • Arigami T.
        • et al.
        Mesothelin expression correlates with prolonged patient survival in gastric cancer.
        J Surg Oncol. 2012; 105: 195-199
        • Yen M.J.
        • Hsu C.Y.
        • Mao T.L.
        • et al.
        Diffuse mesothelin expression correlates with prolonged patient survival in ovarian serous carcinoma.
        Clin Cancer Res. 2006; 12: 827-831
        • Einama T.
        • Homma S.
        • Kamachi H.
        • et al.
        Luminal membrane expression of mesothelin is a prominent poor prognostic factor for gastric cancer.
        Br J Cancer. 2012; 107: 137-142
        • Roe O.D.
        • Creaney J.
        • Lundgren S.
        • et al.
        Mesothelin-related predictive and prognostic factors in malignant mesothelioma: a nested case-control study.
        Lung Cancer. 2008; 61: 235-243
        • Wang L.
        • Niu Z.
        • Zhang L.
        • et al.
        Clinicopathological significance of mesothelin expression in invasive breast cancer.
        J Int Med Res. 2012; 40: 909-916
        • Rakha E.A.
        • Putti T.C.
        • Abd El-Rehim D.M.
        • et al.
        Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation.
        J Pathol. 2006; 208: 495-506
        • Nguyen P.L.
        • Taghian A.G.
        • Katz M.S.
        • et al.
        Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy.
        J Clin Oncol. 2008; 26: 2373-2378
        • Rakha E.A.
        • Reis-Filho J.S.
        • Ellis I.O.
        Basal-like breast cancer: a critical review.
        J Clin Oncol. 2008; 26: 2568-2581
        • Kennecke H.
        • Yerushalmi R.
        • Woods R.
        • et al.
        Metastatic behavior of breast cancer subtypes.
        J Clin Oncol. 2010; 28: 3271-3277
        • Tchou J.
        • Wang L.C.
        • Selven B.
        • et al.
        Mesothelin, a novel immunotherapy target for triple negative breast cancer.
        Breast Cancer Res Treat. 2012; 133: 799-804
        • Tabernero J.
        • Rojo F.
        • Calvo E.
        • et al.
        Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumors.
        J Clin Oncol. 2008; 26: 1603-1610
        • McCarty Jr., K.S.
        • Miller L.S.
        • Cox E.B.
        • et al.
        Estrogen receptor analyses: correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies.
        Arch Pathol Lab Med. 1985; 109: 716-721
        • Shousha S.
        • Peston D.
        Immunohistochemical demonstration of oestrogen and progesterone receptors in paraffin sections of breast carcinoma.
        Curr Diag Pathol. 1997; 4: 176-180
        • Ordonez N.G.
        Value of mesothelin immunostaining in the diagnosis of mesothelioma.
        Mod Pathol. 2003; 16: 192-197
        • Hammond M.E.
        • Hayes D.F.
        • Dowsett M.
        • et al.
        American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer.
        J Clin Oncol. 2010; 28: 2784-2795
        • Raghav K.P.
        • Hernandez-Aya L.F.
        • Lei X.
        • et al.
        Impact of low estrogen/progesterone receptor expression on survival outcomes in breast cancers previously classified as triple negative breast cancers.
        Cancer. 2012; 118: 1498-1506
        • Hassan R.
        • Bera T.
        • Pastan I.
        Mesothelin: a new target for immunotherapy.
        Clin Cancer Res. 2004; 10: 3937-3942
        • Hassan R.
        • Cohen S.J.
        • Phillips M.
        • et al.
        Phase I clinical trial of the chimeric anti-mesothelin monoclonal antibody MORAb-009 in patients with mesothelin-expressing cancers.
        Clin Cancer Res. 2010; 16: 6132-6138
        • Kelly R.J.
        • Sharon E.
        • Pastan I.
        • et al.
        Mesothelin-targeted agents in clinical trials and in preclinical development.
        Mol Cancer Ther. 2012; 11: 517-525
        • Ma J.
        • Tang W.K.
        • Esser L.
        • et al.
        Recognition of mesothelin by the therapeutic antibody MORAb-009: structural and mechanistic insights.
        J Biol Chem. 2012; 287: 33123-33131
        • Wang K.
        • Bodempudi V.
        • Liu Z.
        • et al.
        Inhibition of mesothelin as a novel strategy for targeting cancer cells.
        PLoS One. 2012; 7: e33214