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The expression and prognostic significance of bcl‐2‐associated transcription factor 1 in rectal cancer following neoadjuvant therapy
Author(s) -
Brown Gordon T,
Cash Beatriz,
Alnabulsi Ayham,
Samuel Leslie M,
Murray Graeme I
Publication year - 2016
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12780
Subject(s) - colorectal cancer , immunohistochemistry , tissue microarray , cancer research , cancer , biology , oncology , pathology , medicine
Aims bcl‐2‐associated transcription factor 1 ( BCLAF 1) 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 BCLAF 1 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 BCLAF 1 that we have developed was used. Non‐neoplastic rectal epithelium showed nuclear localization of BCLAF 1 in both crypt and surface epithelial cells, whereas rectal cancers showed both nuclear and cytoplasmic BCLAF 1 expression. Most rectal cancers showed moderate or strong nuclear immunoreactivity, but showed weak cytoplasmic immunoreactivity. Cytoplasmic BCLAF 1 expression was increased in primary rectal cancers as compared with non‐neoplastic rectal mucosa ( P = 0.008). Negative and weak nuclear BCLAF 1 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 BCLAF 1 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 BCLAF 1 expression and nuclear BCLAF 1 expression are increased in post‐neoadjuvant therapy rectal cancer, and that negative and weak nuclear BCLAF 1 expression are independently associated with a poor prognosis.