title: Increased pSmad2 expression and cytoplasmic predominant presence of TGF-βRII in breast cancer tissue are associated with poor prognosis: results from the Shanghai Breast Cancer Study.
abstract: Perturbations of transforming growth factor-beta (TGF-β) signaling are pivotal to tumorigenesis and tumor progression through their effects on cell proliferation and cell invasion. This study aims to evaluate the association of TGF-βRII and pSmad2 protein expressions in breast tissue with clinicopathological factors and prognosis of breast cancer. Expression of the TGF-βRII and pSmad2 proteins was assessed in breast tissue of 1,045 breast cancer cases in the Shanghai Breast Cancer Study using a double immunofluorescence staining method, which was validated with standard single immunostains. TGF-βRII expression intensity was positively associated with younger age at diagnosis (P = 0.03), pre-menopausal status (P = 0.03), and lower TNM stage (P = 0.04). Cytoplasmic predominant expression pattern of TGF-βRII was associated with older age at diagnosis (P = 0.04) and invasive histological type (P = 0.03). Increased pSmad2 expression was associated with higher breast cancer grade (P < 0.01). Higher pSmad2 expression [HR (95 % CI):1.48 (1.07-2.04), P = 0.02] and cytoplasmic predominant TGF-βRII expression [HR (95 % CI): 1.80 (1.08-3.00), P = 0.02] were significantly associated with reduced cancer-free survival. Our data suggest that TGF-βRII and pSmad2 expressions are associated with certain clinical and pathologic features of breast cancer. A cytoplasmic predominant TGF-βRII expression pattern and a higher pSmad2 expression were associated with decreased breast cancer survival. Our study provides additional evidence to support the important role of TGF-β signaling in breast cancer prognosis.
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 1161 21st Avenue South, Nashville, TN, 37232, USA.
authors.forename: Qingchao
authors.initials: Q
authors.lastname: Qiu
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Su
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.forename: Shenghui
authors.initials: S
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Xiao Ou
authors.initials: XO
authors.lastname: Shu
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D002681:China; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D047368:Tumor Burden
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II