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Analysis of SHIP2 Expression and its Correlation with VEGF and HER-2 Expression in Breast Cancer

Han H, Wang B, Zhao J, Xu G, Wang X and Cao F

Purpose: To investigate SHIP2 expression in breast cancer tissues, and its correlation with clinicopathological features and with the expressions of VEGF and HER-2 in cancer tissues.

Methods: Immunohistochemical staining for SHIP2, HER-2 and VEGF was performed on paraffin-embedded tissue specimens, including 80 specimens of breast cancer and 53 adjacent tissue samples. Two pathologists were invited to interpret the immunohistochemistry results using double-blind method. Expression profiles of SHIP2, HER-2 and VEGF were evaluated and scored according to percentage of positive cells and positive signal intensity. The correlation between SHIP2 and clinicopathological features was analyzed by chi-square test and fourfold table exact test. The correlation among SHIP2, HER-2 and VEGF expression were analyzed using Pearson contingency coefficient analysis for evaluating prognostic relevance to breast cancer.

Results: The positive expression rates of SHIP2, HER-2 and VEGF were significantly higher than that of adjacent normal tissues (p<0.05). SHIP2 expression was significantly increased, in the case of the four risk factors (the poor histological grade, the later stages, lymph node metastasis, and higher BMI) (p<0.05). Positive rate of both SHIP2 and VEGF protein expression indicated a significant correlation between the two proteins (r=0.30, p<0.05). In addition, in the HER-2 protein positive group, SHIP2 protein expression also showed a positive correlation (r=0.71, p<0.05) between these two proteins. Expression of all three proteins were highly related to tumor histopathologic grade, clinical terms, and lymphatic metastasis (p<0.05). Our data indicates that SHIP2 expression in tumor tissue is significantly correlated with HER-2 and VEGF expression.

Conclusion: Our study provides a proof of concept that SHIP2, correlated with HER-2 and VEGF, plays important roles in tumorigenesis, infiltration, and metastasis of breast cancer, and are highly associated with prognosis.

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