Expression Of HSP90B1 And Moesin And Their Significance In Invasive Ductal Breast Carcinoma

[Objective] Breast cancer is one of the most common malignant tumors in women. The survival was significantly improved since the 1990s because of the surgery、 neoadjuvant chemotherapy,and targeted therapy development and the aromatase inhibitors for breast cancer patients. However, once distant metastases occered, it would mean failure of the treatment on breast cancer patients,and even cause to death. In this study, we selected two proteins Heat Shock Protein (HSP) 90B1 and Moesin (membrane-organizing extension spike protein), from 45 filtered proteins by proteins electrophoresis and mass spectrometry,which are considered as having relationship to lymph node metastasis in breast cancer,and collected a large sample of patients with follow-up data. We want to investigate the expressions of HSP90B1 and Moesin in invasive ductal breast carcinoma and their correlations with clinicopatho-logical features,especially with lymph node metastasis and distant metastasis.[Methods] Archival tissue blocks of 236 cases with invasive breast ductal carcinoma in Linyi Tumor Hospital from March 2005 to December 2008 were continually collected. Tissue microarray (TMA) and immunohistochemical(IHC) streptavidin-perosidase(S-P) technologies were used to evaluate expression of HSP90B1 and Moesin in 236 cases.At the same time the clinicopathologic and follow-up information have been collected. The relationship between HSP90B1 and Moesin expression and clinicopathologic features were analyzed using SPSS 13.0 statistical software with x2 test, rank test, Spearman rank correlation analysis.Using Kaplan-Meier method to observe the relationship between the expression of Moesin and HSP90B1 and the patient’s DFS and OS.[Results] 1.HSP90B1 expression was positive in 65.3% of all 236 cases (154/236), significantly higher than in adjacent cancer tissue, mammary fibroma, benign hyperplasia breast tissue. ① It is higher in patients with tumor size(>2cm),grade(Ⅱ, Ⅲ), negative estrogen and progesterone receptor, positive Her-2, axillary lymph node metastasis and recurrence/distant metastasis than in patients with tumor size(<2cm),grade(Ⅰ), positive estrogen and progesterone receptor, negative Her-2 and no recurrence/metastasis (P<0.05). ② The expression of HSP90B1 was positively correlated with tumor size, histological grade, expression of Her-2, axillary lymph node metastasis and recurrent/metastastic cases while negatively correlated with ER and PR expression. ③Furthermore, the expression of HSP90B1 in luminal A group was lower than in HER2+ group and triple negative group(P<0.05) and there was no significantly difference between other groups. ④ The patients with negative HSP90B1 had better disease-free survival (DFS) and overall survival than patients with positive HSP90B1 (P=0.027,0.048,respectively).2.Moesin expression was positive in 65.7% of all 236 cases (155/236), significantly-higher than in adjacent cancer tissue, mammary fibroma, benign hyperplasia breast tissue (P<0.05). ① It is higher in patients with negative estrogen and progesterone receptor and recurrence/distant metastasis than in patients with positive estrogen and progesterone receptor and without recurrence/metastasis (P<0.05). ② The expression of Moesin was positively correlated with histological grade(r=0.157)and recurrence/distant metastasis (r=0.164) (P<0.05) while negatively correlated with ER (r=-0.205) and PR (r=-0.183) expression (P<0.05), but it had no significant correlation with age, tumor size, status of Her-2 and lymph node metastasis(P>0.05). ③The expression of Moesin in Her-2+ group was higher than in LuminalA group and LuminalB group (P=0.002,0.014,respectively) and it was higher in triple negative group than in Luminal A group(P=0.036). There was no significantly difference between other groups(P>0.05). ④The patients with negative Moesin had better DFS compared with positive Moesin (P=0.011)but there is no difference in overall survival(P>0.05).3.The expressions of Moesin were positively correlated with the expressions of HSP90B1 using Spearman test (r=0.297,P=0.000)4.The status of recurrence/distant metastasis was positively correlated with tumor size (r=0.217), the status of axillary lymph node (r=0.236), the expression of HSP90B1 (r=0.143) and Moesin (r=0.164),and negatively correlated with the status of ER (r=-0.137) (P<0.05) in 37 recurrent/distant metastatic cases.[Conclusion] High expression of HSP90B1 in patients with invasive ductal breast cancer predicted a poor prognosis. High expression of Moesin indicated high invasive of tumors with high risk of metastasis/recurrence and it might play an important role in blood metastasis. Our study showed HSP90B1 and Moesin had significantly correlation and further studies may focus on their mechanism and find out how they work.