The expression and prognostic significance of bcl-2-associated transcription factor 1 in rectal cancer following neoadjuvant therapy

Abstract

Aims: bcl-2-associated transcription factor 1 (BCLAF1) is a nuclear protein that binds to bcl-related proteins and can induce apoptosis and autophagy. The aim of this study was to investigate the expression of BCLAF1 in a series of rectal cancers following neoadjuvant therapy.

Methods and results: Immunohistochemistry was performed on a post-neoadjuvant therapy rectal cancer tissue microarray. It contained rectal cancers (n = 248), lymph node metastases (n = 76), and non-neoplastic rectal mucosal samples (n = 73). A monoclonal antibody against BCLAF1 that we have developed was used. Non-neoplastic rectal epithelium showed nuclear localization of BCLAF1 in both crypt and surface epithelial cells, whereas rectal cancers showed both nuclear and cytoplasmic BCLAF1 expression. Most rectal cancers showed moderate or strong nuclear immunoreactivity, but showed weak cytoplasmic immunoreactivity. Cytoplasmic BCLAF1 expression was increased in primary rectal cancers as compared with non-neoplastic rectal mucosa (P = 0.008). Negative and weak nuclear BCLAF1 expression was associated with a poor prognosis [hazard ratio (HR) 0.502, 95% confidence interval (CI) 0.269-0.939, χ(2) = 4.876, P = 0.027]. Nuclear BCLAF1 expression was independently prognostic in a multivariate model (HR 0.431, 95% CI 0.221-0.840, P = 0.013).

Conclusions: This study has shown that both cytoplasmic BCLAF1 expression and nuclear BCLAF1 expression are increased in post-neoadjuvant therapy rectal cancer, and that negative and weak nuclear BCLAF1 expression are independently associated with a poor prognosis.

Keywords: bcl-2-associated transcription factor 1; biomarker; immunohistochemistry; monoclonal antibody; neoadjuvant therapy; prognosis; rectal cancer.