Abstract 2596: Correlation of TGF beta receptor II and pSmad2 expression with clinico-pathological factors in human breast cancer: An immunohistochemical observation from the Shanghai Breast Cancer Study

Abstract

Abstract Loss of transforming growth factor (TGF)-α expression occurs in the early stages of breast carcinogenesis, which contributes to tumor progression. The loss of TGF-β responsiveness frequently occurs at the level of the TGF- ≤ receptor II (TGF-βRII) in breast cancer. Smad2 is a major receptor-activated Smad downstream of TGF-β signaling. Phosphorylated Smad2 (pSmad2) is translocated into the nucleus to modulate transcription of target genes involved in many cell functions. We evaluated the correlation of TGF-βRII and pSmad2 protein expression with clinico-pathological factors in human breast cancer tissue from 435 breast cancer cases from the Shanghai Breast Cancer Study, a population-based, case-control study. Expression of the TGF-βRII and pSmad2 proteins was detected using a double immunofluorescence staining method, which was validated with standard single immunostains. Lab-constructed tissue microarray samples were used as positive and negative controls. The immunofluorescence signals were designated as negative, positive, or strong-positive based on a modified Allred scoring system. Staining patterns of TGF-βRII were classified into membranous or cytoplasmic predominant. TGF-βRII expression intensity was significantly higher in normal and early-stage breast cancers (in situ carcinoma) than that in later stages (in situ carcinoma adjacent to invasive carcinoma, and invasive carcinoma) (P<0.001). The cytoplasmic predominant expression pattern of TGF-βRII was more frequently observed in breast cancer than that in normal breast epithelium on the same tissue section (P<0.001). pSmad2 expression was significantly increased in breast cancer compared with adjacent normal breast epithelium. In addition, the increased pSmad2 expression was significantly associated with higher breast cancer grade (P=0.004). No significant correlations between TGF-βRII/pSmad2 protein expression and other prognostic factors, such as age at diagnosis, menopause status, history of breast cancer, TNM stage, and ER/PR/HER2 status, was found. The results of this study suggest that reduced TGF-βRII expression and its cytoplasmic predominant expression pattern may be associated with the progression of breast cancer, and increased pSmad2 expression may be associated with carcinogenesis and poor differentiation of breast cancer cells. Additional samples are being analyzed to validate these findings and to evaluate the expression of TGF-βRII and pSmad2 in relation to breast cancer survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2596. doi:1538-7445.AM2012-2596