Overexpression of HIF1α and CAXI predicts poor outcome in early-stage triple negative breast cancer
Autor: | Dong Young Noh, Kyubo Kim, Han Suk Ryu, Wonshik Han, Min Sun Jin, Seock-Ah Im, Hyebin Lee, In Ae Park, Yul Ri Chung, Hyeong-Gon Moon, Tae Yong Kim, Kyung Hun Lee |
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Rok vydání: | 2016 |
Předmět: |
Adult
0301 basic medicine Oncology Pathology medicine.medical_specialty Cyclophosphamide medicine.medical_treatment Triple Negative Breast Neoplasms Biology Disease-Free Survival Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Breast cancer Antigens Neoplasm Internal medicine Biomarkers Tumor medicine Humans Carbonic Anhydrase IX Molecular Biology Triple-negative breast cancer Aged Carbonic Anhydrases Neoplasm Staging Chemotherapy Tissue microarray Cell Biology General Medicine Middle Aged Hypoxia-Inducible Factor 1 alpha Subunit Prognosis medicine.disease Radiation therapy Early Diagnosis 030104 developmental biology 030220 oncology & carcinogenesis Immunohistochemistry Female medicine.drug |
Zdroj: | Virchows Archiv. 469:183-190 |
ISSN: | 1432-2307 0945-6317 |
Popis: | Dysregulated energy metabolism is one of the main mechanisms for uncontrolled growth in solid tumors. Hypoxia-inducible factor 1-alpha (HIF1α) is a transcription factor implicated in regulating several genes that are responsible for cell metabolism, including carbonic anhydrase IX (CAIX). The aim of this study is to determine the clinical significance of immunohistochemical metabolic alteration in early-stage triple negative breast cancer (TNBC) patients who received cyclophosphamide-based chemotherapy or radiotherapy and those with basal phenotype. Immunohistochemical staining for HIF1α and CAIX was performed to determine the correlation with clinicopathologic variables and survival outcome on tissue microarrays from 270 early-stage TNBC patients. In vitro experiments with multiple human TNBC cell lines, suppression of HIF1α by small interfering RNA (siRNA) significantly reduced CAIX protein expression in all cell lines. In multivariate analyses for different therapeutic modalities and basal phenotype, combined HIF1α and CAIX protein overexpression was significantly associated with disease-free survival in the total cohort (OR = 2.583, P = 0.002), stratified cohorts expressing basal phenotype (OR = 2.234, P = 0.021), and in those patients who received adjuvant chemotherapy (OR = 3.078, P = 0.023) and adjuvant radiotherapy (OR = 2.111, P = 0.050), respectively. In early TNBC, combined HIF1α and CAIX protein expression may serve as an unfavorable prognostic indicator particularly in patients treated with cyclophosphamide-based chemotherapy or radiotherapy as well as those with basal phenotype of breast cancer. |
Databáze: | OpenAIRE |
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