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Expression of FOXM 1 and related proteins in breast cancer molecular subtypes
Author(s) -
Lee JeongJu,
Lee Hee Jin,
Son ByungHo,
Kim SungBae,
Ahn JinHee,
Ahn Seung Do,
Cho Eun Yoon,
Gong Gyungyub
Publication year - 2016
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12187
Subject(s) - breast cancer , cancer , biology , cancer research , microbiology and biotechnology , genetics
Summary Forkhead box ( FOX ) proteins constitute an extended family of transcriptional regulators. FOXM 1 is ubiquitously expressed in cells undergoing proliferation, and overexpression of FOXM 1 is associated with poor prognosis in various malignant tumours. FOXM 1 and FOXO 3a are often transcriptionally antagonistic. FOXO 3a plays a critical tumour‐suppressive role in breast cancer. FOXO activity is modulated by its acetylation status, which is regulated by class III histone deacetylases (sirtuins; also known as SIRT s). This study evaluated the role of FOX proteins and their regulators in each molecular subtype of breast cancer. Immunohistochemical expressions of FOXM 1, FOXO 3a, SIRT 1 and SIRT 6 were evaluated in tissue microarray blocks containing 688 consecutive breast cancer samples. Mean expression levels were used to categorize tumours according to the expression of each protein (high or low). High expression of FOXM 1 was significantly correlated with high SIRT 1 and SIRT 6 expression, higher histologic grade and triple‐negative breast cancer ( TNBC ). High expression of nuclear FOXO 3a and nuclear SIRT 1 was correlated with a lower histologic grade and the hormone receptor‐positive/ HER 2‐negative subtype. In survival analysis, FOXM 1 was an independent adverse prognostic factor for disease‐free and overall survival in the hormone receptor‐positive/ HER 2‐negative subtype but not in the HER 2‐positive subtype or TNBC . In conclusion, although high FOXM 1 expression was noted in the TNBC subtype, it had no prognostic impact in TNBC . However, it had prognostic significance in the hormone receptor‐positive/ HER 2‐negative subtype.