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
AUTOR(ES)
Tiezzi, Daniel Guimarães, Clagnan, Willian Simões, Mandarano, Larissa Raquel Mouro, de Sousa, Christiani Bisinoto, Marana, Heitor Ricardo Cosiski, Tiezzi, Marcelo Guimarães, de Andrade, Jurandyr Moreira
FONTE
Clinics
DATA DE PUBLICAÇÃO
2013-05
RESUMO
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.
Documentos Relacionados
- Expression of Hypoxia-inducible factor 1-α and Vascular endothelial growth factor-C in locally advanced breast cancer patients
- Hypoxia-inducible factor-1α and -2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis
- Hypoxia-inducible factor 1 alpha in high-risk breast cancer: an independent prognostic parameter?
- Expression of hypoxia-inducible factor-1α and cell cycle proteins in invasive breast cancer are estrogen receptor related
- Expression of LRP and MDR1 in locally advanced breast cancer predicts axillary node invasion at the time of rescue mastectomy after induction chemotherapy