Value of immunohistochemical detection of FOXO3a as a prognostic marker in human breast carcinoma

Breast cancer is the most common neoplasm in women. Forkhead box-O (FOXO) transcription factors act as transcriptional regulators in the nucleus by modulating cell differentiation, cell cycle arrest, and apoptosis. Based on the their ability to control cell cycle and apoptosis, FOXOs may be a useful prognostic biomarker for breast cancer. Thus, we aimed to investigate the expression patterns of FOXO3a in human breast cancer tissue, immunohistochemically and to evaluate the whether a relationship between FOXO3a and the prognostic factors of breast tumor. FOXO3a expression patterns were examined in thirty tissue specimens from patients with primary operable breast carcinoma who underwent mastectomy. The score of cytoplasmic staining were ranged from 3 to 4 and the score of nuclear staining were ranged from 0 to 3. 100% of specimens showed cytoplasmic staining, 80% of specimens showed both cytoplasmic and nuclear staining and 20% of specimens showed no nuclear staining. FOXO3a nuclear staining scores showed negative correlation with grade, stage, metastatic axillary lymph node, HER2 score, and Ki-67 proliferative index (P = 0.02, P < 0.001, P < 0.001, P < 0.001, P = 0.003, respectively) and a positive correlation with estrogen receptor (P = 0.012). There was not found a relationship between between clinicopathological parameters and cytosplasmic staining scores. Consequently, the nuclear FOXO3a accumulation appears to be closely associated with the malignancy of breast tumors. Therefore, consideration of the nuclear FOXO3a staining pattern rather than cytoplasmic staining or total staining pattern will be a more useful prognostic biomarker for breast cancer.