title: Loss of stromal caveolin-1 expression predicts poor clinical outcome in triple negative and basal-like breast cancers.
abstract: Here, we investigated the possible predictive value of stromal caveolin-1 (Cav-1) as a candidate biomarker for clinical outcome in triple negative (TN) breast cancer patients. A cohort of 85 TN breast cancer patients was available, with the necessary annotation and nearly 12 years of follow-up data. Our primary outcome of interest in this study was overall survival. Interestingly, TN patients with high-levels of stromal Cav-1 had a good clinical outcome, with >50% of the patients remaining alive during the follow-up period. In contrast, the median survival for TN patients with moderate stromal Cav-1 staining was 33.5 months. Similarly, the median survival for TN patients with absent stromal Cav-1 staining was 25.7 months. A comparison of 5-year survival rates yields a similar pattern. TN patients with high stromal Cav-1 had a good 5-year survival rate, with 75.5% of the patients remaining alive. In contrast, TN patients with moderate or absent stromal Cav-1 levels had progressively worse 5-year survival rates, with 40 and 9.4% of the patients remaining alive. In contrast, in a parallel analysis, the levels of tumor epithelial Cav-1 had no prognostic significance. As such, the prognostic value of Cav-1 immunostaining in TN breast cancer patients is compartment-specific, and selective for an absence of Cav-1 staining in the stromal fibroblast compartment. A recursive-partitioning algorithm was used to assess which factors are most predictive of overall survival in TN breast cancer patients. In this analysis, we included tumor size, histologic grade, whether the patient received surgery, radiotherapy or chemotherapy, CK5/6, EGFR, p53 and Ki67 status, as well as the stromal Cav-1 score. This analysis indicated that stromal loss of Cav-1 expression was the most important prognostic factor for overall survival in TN breast cancer. Virtually identical results were obtained with CK5/6 (+) and/or EGFR (+) TN breast cancer cases, demonstrating that a loss of stromal Cav-1 is also a strong prognostic factor for basal-like breast cancers. Our current findings may have important implications for the close monitoring and treatment stratification of TN and basal-like breast cancer patients.
authors.affiliation: Department of Pathology, Jefferson Center for Pancreatic, Biliary and Related Cancers, Thomas Jefferson University, Philadelphia, PA, USA. agnieszka.witkiewicz@jefferson.edu
authors.forename: Agnieszka K
authors.initials: AK
authors.lastname: Witkiewicz
authors.forename: Abhijit
authors.initials: A
authors.lastname: Dasgupta
authors.forename: Sara
authors.initials: S
authors.lastname: Sammons
authors.forename: Ozlem
authors.initials: O
authors.lastname: Er
authors.forename: Magdalena B
authors.initials: MB
authors.lastname: Potoczek
authors.forename: Fran
authors.initials: F
authors.lastname: Guiles
authors.forename: Federica
authors.initials: F
authors.lastname: Sotgia
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Brody
authors.forename: Edith P
authors.initials: EP
authors.lastname: Mitchell
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D051242:Caveolin 1 / Q000378:metabolism*; D015331:Cohort Studies; D003238:Connective Tissue / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D053555:Keratin-5 / Q000378:metabolism; D053553:Keratin-6 / Q000378:metabolism; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000032:analysis; D018709:Statistics, Nonparametric; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D051242:Caveolin 1; D066246:ErbB Receptors; D053555:Keratin-5; D053553:Keratin-6; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone