J Korean Med Sci.  2015 Apr;30(4):390-397. 10.3346/jkms.2015.30.4.390.

Increased Expression of Forkhead Box M1 Is Associated with Aggressive Phenotype and Poor Prognosis in Estrogen Receptor-Positive Breast Cancer

• Ahn H
• Sim J
• Abdul R
• Chung MS
• Paik SS
• Oh YH
• Park CK
• Jang K

• KMID: 2164446
• DOI: http://doi.org/10.3346/jkms.2015.30.4.390

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.

Keyword

Breast Neoplasms; Forkhead Transcription Factor; Foxhead Box M1; Foxhead Box O3a; Prognosis

MeSH Terms

Breast Neoplasms/chemistry/mortality/*pathology
Female
Forkhead Transcription Factors/*analysis
Humans
Phenotype
Prognosis
Receptor, ErbB-2/analysis
Receptors, Estrogen/*analysis
Forkhead Transcription Factors
Receptor, ErbB-2
Receptors, Estrogen

Figure

• 

  Fig. 1 Representative sections of the immunohistochemistry of FoxM1 and FoxO3a in breast cancer tissue (magnification, × 400). (A) Negative FoxM1 staining. (B) Weak FoxM1 staining. (C) Intermediate FoxM1 staining. (D) Strong FoxM1 staining. (E) Negative FoxO3a staining. (F) Weak FoxO3a staining. (G) Intermediate FoxO3a staining. (H) Strong FoxO3a staining.

• 

  Fig. 2 Kaplan-Meier curves for disease-free and overall survival for breast cancer according to FoxM1 expression.

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