title: Increased expression of forkhead box M1 is associated with aggressive phenotype and poor prognosis in estrogen receptor-positive breast cancer.
abstract: Fox transcription factors play a critical role in the regulation of a variety of biological processes. While FoxM1 behaves like the oncogenic transcription factor, FoxO3a is known as a tumor suppressor by inhibiting FoxM1. This study aimed to investigate the clinicopathological significance of FoxM1 and FoxO3a expression in breast cancer. Expression of FoxM1 and FoxO3a were analyzed by immunohistochemical staining on tissue microarray sections from 236 breast cancer patients, and correlated with various clinicopathological characteristics. Overexpression of FoxM1 correlated with adverse clinicopathological features, such as larger tumor size, lymph node metastasis, advanced tumor stage, and lymphovascular invasion. The Kaplan-Meier survival curves revealed no prognostic significance of FoxM1 expression. However, in subgroup analyses with patients of estrogen receptor (ER) positive breast cancers, FoxM1 overexpression associated with poor disease free and overall survival. No association was found between FoxO3a and FoxM1 expression. Regarding clinicopathological variables, the only association between histologic grade and FoxO3a was observed. In conclusion, FoxM1 overexpression was significantly associated with aggressive phenotypes and poor prognosis of ER-positive breast cancer. These findings suggest the possible role of FoxM1 as a prognostic biomarker and putative target of anti-cancer therapy.
authors.affiliation: Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Hyein
authors.identifier: 0000-0001-9221-672X
authors.initials: H
authors.lastname: Ahn
authors.affiliation: Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Jongmin
authors.identifier: 0000-0002-7106-1279
authors.initials: J
authors.lastname: Sim
authors.affiliation: Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Rehman
authors.identifier: 0000-0003-4223-4545
authors.initials: R
authors.lastname: Abdul
authors.affiliation: Department of Surgery, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Min Sung
authors.identifier: 0000-0001-5086-3718
authors.initials: MS
authors.lastname: Chung
authors.affiliation: Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Seung Sam
authors.identifier: 0000-0002-8607-4072
authors.initials: SS
authors.lastname: Paik
authors.affiliation: Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Young-Ha
authors.identifier: 0000-0001-8750-9843
authors.initials: YH
authors.lastname: Oh
authors.affiliation: Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Chan Kum
authors.identifier: 0000-0002-8495-720X
authors.initials: CK
authors.lastname: Park
authors.affiliation: Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Kiseok
authors.identifier: 0000-0002-6585-3990
authors.initials: K
authors.lastname: Jang
mesh_terms: D001943:Breast Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D005260:Female; D000072278:Forkhead Box Protein M1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006801:Humans; D010641:Phenotype; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis*
chemical_list: D000072278:Forkhead Box Protein M1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C107585:FOXM1 protein, human; C499517:FOXO3 protein, human; C508053:ERBB2 protein, human
keywords: Breast Neoplasms; Forkhead Transcription Factor; Foxhead Box M1; Foxhead Box O3a; Prognosis
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