title: Upregulation of HSF1 in estrogen receptor positive breast cancer.
abstract: Heat shock transcription factor 1 (HSF1), a key regulator of the heat-shock response, is deregulated in many cancers. HSF1 can mediate cancer cell survival and metastasis. High levels of HSF1 have been associated with poor prognosis in breast cancer. The nature of HSF1 upregulation needs to be validated in different cohorts to further validate its prognostic utility in breast cancer.We first evaluated its expression in a cohort of breast cancer tissue microarrays with Oncotype DX recurrence scores available using immunohistochemistry. To further confirm the clinical relevance and prognostic impact, mutational and methylation status of the gene were also assessed in The Cancer Genome Atlas and publically available microarray datasets.Immunohistochemical analysis showed that HSF1 expression is independent of Oncotype DX high recurrence score in ER-positive node-negative patients. Analysis of The Cancer Genome Atlas data revealed upregulation of HSF1 is not due to methylation or mutation. HSF1 copy number variations and amplifications (15%) were not associated with survival. In publicly available microarray datasets, a prognostic impact was observed in ER-positive tumors, but not in ER-negative tumors. Patients with ER-positive tumors with high HSF1 levels were associated with shorter overall survival (P = 0.00045) and relapse-free survival (P = 0.0057). In multivariable analysis, HSF1 remained a significant prognostic parameter.The mRNA expression levels of HSF1 in ER-positive breast cancer are associated with both shorter relapse-free and overall survival. This prognostic impact is specific to mRNA expression, but stayed insignificant by protein expression or by analyzing amplification events.
authors.affiliation: Departments of Pathology and Laboratory Medicine, Indianapolis, IN.
authors.forename: Yesim
authors.initials: Y
authors.lastname: Gökmen-Polar
authors.affiliation: Departments of Pathology and Laboratory Medicine, Indianapolis, IN.|Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.|Departments of Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN.
authors.forename: Sunil
authors.initials: S
authors.lastname: Badve
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D019175:DNA Methylation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D000076249:Heat Shock Transcription Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D011960:Receptors, Estrogen
keywords: Breast cancer; HSF1; endocrine resistance; estrogen receptor; genomics