Expression of FOXM1 and related proteins in breast cancer molecular subtypes.
Forkhead box (FOX) proteins constitute an extended family of transcriptional regulators. FOXM1 is ubiquitously expressed in cells undergoing proliferation, and overexpression of FOXM1 is associated with poor prognosis in various malignant tumours. FOXM1 and FOXO3a are often transcriptionally antagonistic. FOXO3a 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 SIRTs). This study evaluated the role of FOX proteins and their regulators in each molecular subtype of breast cancer. Immunohistochemical expressions of FOXM1, FOXO3a, SIRT1 and SIRT6 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 FOXM1 was significantly correlated with high SIRT1 and SIRT6 expression, higher histologic grade and triple-negative breast cancer (TNBC). High expression of nuclear FOXO3a and nuclear SIRT1 was correlated with a lower histologic grade and the hormone receptor-positive/HER2-negative subtype. In survival analysis, FOXM1 was an independent adverse prognostic factor for disease-free and overall survival in the hormone receptor-positive/HER2-negative subtype but not in the HER2-positive subtype or TNBC. In conclusion, although high FOXM1 expression was noted in the TNBC subtype, it had no prognostic impact in TNBC. However, it had prognostic significance in the hormone receptor-positive/HER2-negative subtype.
Department of Pathology, Seonam University College of Medicine, Myongji Hospital, Deokyang-gu, Goyang, Korea.
Jeong-Ju
JJ
Lee
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Seoul, Korea.
Hee Jin
HJ
Lee
Department of Pathology Surgery, University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Seoul, Korea.
Byung-Ho
BH
Son
Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Seoul, Korea.
Sung-Bae
SB
Kim
Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Seoul, Korea.
Jin-Hee
JH
Ahn
Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Seoul, Korea.
Seung Do
SD
Ahn
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Korea.
Eun Yoon
EY
Cho
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Seoul, Korea.
Gyungyub
G
Gong
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D000072278:Forkhead Box Protein M1 / Q000378:metabolism*; D000071316:Forkhead Box Protein O3 / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000378:metabolism; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism; D037761:Sirtuins / Q000378:metabolism; D055815:Young Adult
D014408:Biomarkers, Tumor; D000072278:Forkhead Box Protein M1; D000071316:Forkhead Box Protein O3; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D056564:Sirtuin 1; D037761:Sirtuins; C107585:FOXM1 protein, human; C499517:FOXO3 protein, human; C508053:ERBB2 protein, human; C447939:SIRT1 protein, human; C516592:SIRT6 protein, human
FOXM1; FOXO3a; Forkhead box protein; SIRT1; SIRT6; breast cancer; prognosis