| Purpose: Invasive micropapillary carcinoma(IMPC)of the breast has distinct histological features and molecular genetic profiles.High-level gains/amplifications of 8q24 are significantly associated with IMPC.Although the prostate stem cell antigen(PSCA)gene lies within chromosome 8q24,and over-expressed in our prescent study,its alteration during IMPC tumorigenesis has not been well studied.Methods: To assess the prevalence of copy number gains of the PSCA gene,fluorescence in situ hybridization(FISH)was used to analyze IMPC.Results: 1.When PSCA / CEP8 ratio?2,the amplification rates of IMPC group and IDC-NOS group were 60% and 42.9%,respectively.The mean of PSCA / CEP8 ratio in the three groups were 2.93,2.17 and 0.63,respectively.The mean of PSCA / CEP8 ratio in IMPC group and IDC-NOS were higher than those in ILC group(P = 0.004,P = 0.04).2.In order to verify that PSCA overexpression was due to PSCA gene amplification,we selected 22 samples for FISH and immunohistochemical staining simultaneously.The results showed that almost all of the amplified cases showed PSCA protein overexpression,the positive rate of protein expression was 40.9%.3.184 cases of breast cancer were 56 cases of IMPC,72 cases of IDC-NOS,56 cases of ILC.The lymph node metastasis rate in the IMPC group was 69.6%(n = 39),45.8%(n = 33)in the IDC-NOS group,and 41.4%(n = 23)in the ILC group.There was a significant difference in the lymph node metastasis rate between the IMPC group and the IDC-NOS / ILC group(P = 0.007,P = 0.002).).4.The positive rate of PSCA was 58.9%(n = 33)in the IMPC group and 40.3%(n = 29)in the IDC-NOS group.The positive rate of PSCA in ILC group was 3.6%(n = 2).We found a case of mixed invasive ductal lobular carcinoma,PSCA in this case showed heterogeneous expression,IDC-NOS region was positive expression,and weak expression in the ILC region.5.In the patients with IMPC of lymph node metastasis,the expression of PSCA protein was significantly correlated with lymph node metastasis(r = 0.317,P =0.017).6.Kaplan-Meier survival analysis results shows that PSCA positive expression of IMPC group with disease-free survival was significantly lower than PSCA-negative patients(P = 0.003);72 cases of IDC-NOS patients followed up to 2015,the survival rate of patients with PSCA positive expression in IDC-NOS was lower than that in negative patients.The results of Kaplan-Meier survival analysis showed that the survival rate of patients with PSCA positive expression was lower than that of negative expression.The factors influencing the prognosis of IMPC patients,PSCA,lymph node status,age,tumor size and p TNM staging were analyzed by univariate analysis and Cox risk proportional regression model.Univariate analysis showed that PSCA and lymph node scores were correlated with DFS(P = 0.003,P = 0.001).Lymph node grading(95% confidence interval: 1.102-3.117,P = 0.022)was associated with DFS in IMPC patients in multivariate analysis(PSCA)(95% confidence interval: 1.304-32.145,P = 0.020).Conclusions: 1.Our results indicate that PSCA is an attractive target in the 8q24 amplicon.2.Amplification of PSCA gene resulted in high expression of PSCA in IMPC.3.The expression of PSCA was positively correlated with lymph node metastasis in IMPC and IDC-NOS,and its expression might be one of the molecular mechanisms leading to the poor prognosis of IMPC.4.The expression pattern of PSCA in breast cancer is similar to that of E-cad and has significant correlation,so we think that its expression can regulate the expression of cell adhesion molecule E-cad.5.The detection of PSCA protein expression is of great significance to the prognosis prediction and the clinical program.It is important to detect the expression of PSCA protein in predicting prognosis and guiding the clinical treatment.The further study of its mechanism may provide experimental basis for the precision therapy of IMPC. |
PDF Full Text Request