Expression Of Integrin ?1 And Rho GTPases In Invasive Micropapillary Carcinoma Of Breast

Objective The aim of this study was to investigate the expression and significance of Integrin ?1,Rac1,Rho A and Cdc42 in invasive micropapillary carcinoma of breast(IMPC).Methods 89 cases of IMPC was identified in the Department of Breast Cancer Pathology and Research Laboratory,Tianjin Medical University Cancer Hospital between January,2007,and December,2008,and we compared to the cases of 90 cases with IDC-NOS from the same time period.By immunohistochemistry staining(IHC),the expression of Integrin ?1,Rac1,Rho A and Cdc42 were analyzed and we studied the relationship among the four proteins,clinicopathologic characteristics and prognosis in patients with IMPC.Results 1.IMPC had a significant higher lymph node involvement(P < 0.001)compared with IDC-NOS.There was no significant difference in patient age,tumor size,histological grade,ER status,PR status,and HER-2 status between IMPC and IDC-NOS(P > 0.05).2.The high expression of Integrin ?1(78.7%)and Rac1(76.4%)in IMPC were significantly higher than those in IDC-NOS(63.3% and 54.4%),with statistic difference(P <0.05);the positive rate of Rho A(68.5%)in IMPC was higher than that in IDC-NOS(44.4%),also with statistic difference(P =0.001).The group,Cdc42 was positive in 78.7 %(n = 70)and negative in 21.3 %(n = 19);in the IDC-NOS,positive in 83.3%(n = 75)and negative in 16.7 %(n = 15).The expression of Cdc42 78.7 %(n = 70)was lower in the IMPC group than that in the IDC-NOS group,not with statistic difference P = 0.425).3.In IMPC,the expression of Integrin ?1 and Rac1 were both positively associated with lymph node metastasis(P <0.05)and the expression of Integrin ?1 was positively correlated with Rac1 expression(P=0.006);the expression of Rho A was positively correlated with lymph node involvement,ER and PR status(P<0.05),However,the correlation among Rho A expression and the expression of ?1 integrin and Rac1 were failed to be observed(P >0.05).4.Kaplan-Meier analysis revealed that Integrin ?1 and Rac1 expression were correlated with worse outcome in IMPC(P = 0.014,P = 0.035,respectively),As in the IMPC group,Integrin ?1 High and Rac1 High status were significantly associated;we further studied whether a combination of biomarkers was predictive for DFS in this group.The data has shown that patient with the co-expression of Integrin ?1 High /Rac1 High tumor tend to have a shorter DFS than patient with Integrin ?1 High or Rac1 High and co-expression of Integrin ?1 Low /Rac1 Low tumor(P = 0.001).In multivariate analysis,the co-expression of Integrin ?1 High /Rac1 High appeared to predict an unfavorable prognosis in IMPC(HR,4.434;95 % CI,1.067-18.436;P = 0.040).Conclusions 1.IMPC has a higher incidence of axillary lymph node metastases.2.The expression of Integrin ?1,Rac1 and Rho A might make some contribution to the biological behavior of high proclivity for metastasis in IMPC.3.Integrin ?1,Rac1 and Rho A might play an important role in the highly metastatic biological behavior of the IMPC.4.We suspect that Integrin ?1 and Rac1 might be the key factors of the poor prognosis in the IMPC.5.We hypothesized that Integrin ?1 and Rac1 synergistic interaction and could help to lead to the poor prognosis,lead to the formation of the inside-out growth pattern of the IMPC.