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The Expression And Prognostic Value Of P-STAT3in Breast Cancer

Posted on:2015-01-09Degree:MasterType:Thesis
Country:ChinaCandidate:X LiuFull Text:PDF
GTID:2284330431467908Subject:Oncology
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Background and purpose Signal transducers and activators of transcription3(STAT3)protein, latent or inactive in cytoplasm of normal cells, plays an important role inregulating cell growth and differentiation once activated. STAT3appears to be a point ofconvergence for numerous oncogenic signaling pathways. Constitutively activated oramplified STAT3have been observed in a wide number of solid tumors such as lungcancer, breast cancer, prostate cancer, ovarian cancer, gastrointestinal tumors, etc, andhematological cancers. STAT3is considered as an oncoprotein that participates in theprocess of tumor malignant transformation,cancer cell proliferation, differentiation,apoptosis and invasion. While, most of these conclusions are made through experimentsfrom breast cancer cell lines and xenograft models. Studies in humans concerning theinvasion, metastasis or prognosis of breast cancer are relatively limited.The goal of this study was to investigate the expression of phospho-STAT3andidentify the relationship between phospho-STAT3and clinicopathologic features,suchas tumor size, lymph node metastasis, pathological grade, hormone status, etc, as wellas elucidate the prognostic value as a predictor of survival outcomes.Method The expression of p-STAT3was detected in82cases of stage Ⅲ breastcancer by immunohistochemistry and then divided into two groups depending onwhether phospho-STAT3is positively detected or not. The relationship between the expression of phospho-STAT3and other clinicopathologic features,such as tumor size,number of lymph node metastasis, pathological grade, hormone status, etc, as well asthe prognostic value as a predictor of survival outcomes, were analyzed.Results Firstly, the expression rate of phospho-STAT3in breast cancer is38.3%.There was no significant relationship between the expression of phospho-STAT3andother clinicopathologic features,such as age at diagnosis, tumor size, number of lymphnode metastasis, pathological grade, ER status, PR status or Her-2status (P>0.05).Secondly, the disease free survival (DFS) in both3and4yea, as well as the5year overall survival rate (OS) in group phospho-STAT3positively expressed were obviouslyhigher than those in negative group respectively, with ratios compared as follows,87.1%vs.64.7%,82.6%vs.57.5%,83.9%vs.52.9%(P<0.05). Moreover, even after theremoval of patients with negative hormone expression who did not receiveendocrinotherapy, the difference between both4year DFS and5year OS were stillstatically significant (82.1%vs.53.3%,82.6%vs.57.9%, respectively, P<0.05). Thirdly,Kaplan-Meier curves showed noteworthy differences between the positive expression ofphospho-STAT3group and negative one in both disease free survival and overallsurvival (P=0.003,0.032,respectively). Fourthly, multivariate analysis using COXproportional hazards model showed that phoph-STAT3staining was independentlypredictive of disease free survival (P=0.018) with a risk ratio of0.34for positivestaining, while predictive value in overall survival advantage had yet to reach statisticalsignificance (P=0.056) with a risk ratio of0.30for positive staining. Number of lymphnode metastasis was another important variable with independent prognostic value inboth disease free survival and overall survival (RR=1.77,2.08, respectively, P<0.05)Conclusion1. The expression percentage of phospho-STAT3in breast cancer is38.3%. There was no significant relationship between the expression of phospho-STAT3and other clinicopathologic features,such as age at diagnosis, tumor size, number oflymph node metastasis, pathological grade, hormone status or Her-2status.2. Its expression is strongly associated with benefit from disease free survival andoverall survival, which indicates that phoph-STAT3could be a marker of good prognosis in breast cancer patients, and even a predictor that people may benefit fromchemotherapy.
Keywords/Search Tags:breast cancer, STAT3, immunohistochemistry, prognosis
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