Expression of aldehyde dehydrogenase after neoadjuvant chemotherapy is associated with expression of hypoxia-inducible factors 1 and 2 alpha and predicts prognosis in locally advanced breast cancer

Author(s)

Daniel Guimarães Tiezzi ^[1] ; Willian Simões Clagnan ^[2] ; Larissa Raquel Mouro Mandarano ^[3] ; Christiani Bisinoto de Sousa ^[3] ; Heitor Ricardo Cosiski Marana ^[3] ; Marcelo Guimarães Tiezzi ^[6] ; Jurandyr Moreira de Andrade ^[3]

Affiliation

^[1] Universidade de São Paulo. Ribeirão Preto School of Medicine. Hospital das Clínicas - Brasil

^[2] Universidade de São Paulo. Ribeirão Preto School of Medicine. Hospital das Clínicas - Brasil

^[3] Univ Sao Paulo, Hosp Clin Ribeirao Preto, Sch Med, Breast Dis Div, Dept Gynecol & Obstet, BR-14049 Ribeirao Preto, SP - Brazil

^[4] Laboratório de Anatomia Patológica e Citopatologia de Presidente Prudente - Brasil

• Document type: Journal article
• Source: Clinics; v. 68, n. 5, p. 592-598, 2013-05-00.

Abstract

OBJECTIVE: To analyze the expression of hypoxia-inducible factors (hypoxia-inducible factor 1A and hypoxia-inducible factor 2A) and aldehyde dehydrogenase proteins in patients with locally advanced breast carcinoma who were subjected to neoadjuvant chemotherapy. METHODS: We included 90 patients with histologically confirmed stage II and III breast carcinoma who were treated with neoadjuvant chemotherapy between 2000 and 2005. Immunohistochemistry for aldehyde dehydrogenase, hypoxia-inducible factor 1A, and hypoxia-inducible factor 2A was performed before and after neoadjuvant chemotherapy. We analyzed the influence of clinical and pathological features on clinical and pathological response, disease-free survival, and overall survival. RESULTS: An objective clinical response to neoadjuvant chemotherapy was observed in 80% of patients, with 12% showing a complete pathological response. Among all clinical and pathological parameters, only the expression of hypoxia-inducible factor 1A was associated with a pathological response. A positive association was found between expression of aldehyde dehydrogenase and that of hypoxia-inducible factor 1A before and after chemotherapy. Aldehyde dehydrogenase expression was associated with expression of hypoxia inducible-factor 2A in tumors after neoadjuvant treatment. In a univariate analysis, prognosis was influenced by age, pathological response, metastasis to axillary lymph nodes after neoadjuvant chemotherapy, overexpression of hypoxia-inducible factor 2, and the presence of aldehyde dehydrogenase-positive cells within the primary tumor after neoadjuvant chemotherapy. In a multivariate analysis, only age and the presence of aldehyde dehydrogenase-positive cells after chemotherapy were associated with reduced overall survival. CONCLUSION: The presence of aldehyde dehydrogenase-positive cells within the residual tumor after neoadjuvant chemotherapy is associated with an increase in the expression of hypoxia-inducible factor 2A and with poor prognosis in patients with locally advanced breast cancer. (AU)

• FAPESP's process: 08/09294-9 - Epithelial-mesenchymal transition in breast carcinogenesis
• Grantee: Daniel Guimarães Tiezzi
• Support Opportunities: Regular Research Grants