Expression Of Wntless In Non-special Type Of Invasive Ductal Carcinoma Of Breast And Its Significance

Objective:To investigate the expression of Wntless in non-special type of invasive ductal carcinoma (IDC-NOS) of breast and its significance.Methods:10 normal breast tissues,44 patients primary and paired metastatic tumor samples from Jan.1995 to Jul.2015 and 179 patients’ breast tumor samples from Jan.2005 to Dec. 2012 diagnosed with IDC-NOS were collected. The clinicopathologic characteristics, including age, menstrual status, clinical staging, recurrence, metastasis and death were recorded. The expressions of ER, PR, Her-2, Ki-67 and Wntless in IDC-NOS were detected by immunohistochemistry and amplification status of Her-2 in 56 cases was examed by fluorescence in situ hybridization. The expressions of mRNA of Wntless in breast cancers, adjacent tissues and normal breast was referred to Oncomine database. Clinicopathological characteristics and expressions of ER, PR, Her-2 and Ki-67 were compared with Wntless which was analyzed by SPSS statistical analysis system.Result:Histopathologically, IDC-NOS were malignant tumors of varied heterogeneity. The tumor cells showed infiltrative growth and were arranged in nests, cords, trabecular or solid pattern with notable stroma fibrosis and partial tumor necrosis. Cytologically, the tumor cells showed mild to obvious cell polymorphism and nuclear heterogeneity.Immunohistochemically, in normal breast tissues, Wntless showed consistently positive expression in cytoplasm of myoepithelial cells and consistently negative expression in luminal epithelial cells, while Wntless showed varied expression in the cytoplasm of IDC-NOS tumor cells. The overall positive rates of Wntless expression in 179 cases of IDC-NOS were 58.7%. There was no significant difference in age, tumor size, menstrual status, tumor location, tumor histological grade, vascular invasion, lymph node metastasis, molecular typing, PR, Her-2 and clinical stage compared with Wntless expression (P>0.05), while the difference was statistically significant when comparing Wntless expression with normal breast tissues(P<0.05), and expression of ER status(P<0.05). Chi square test showed no significant changes of ER, PR and HER-2, Ki-67 and Wntless expression between 44 primary IDC-NOS and paired metastatic samples, while the expression of Wntless was statistically significant between those with recurrence and those without recurrence in 44 cases of primary site and 179 patients with recurrence status (P<0.05).Spearman’s rank correlation analysis indicated that Wntless expression were negatively correlated with ER (P<0.05), while no statistically significant correlation with PR, Ki-67, HER-2 expression, molecular typing and clinical parameters such as age, tumor size, tumor location, histological grade, vascular invasion, recurrence, lymph node metastasis and clinical pathological staging.Molecular genetic detection (FISH) was performed in 56 cases of 179 IDC-NOS cases and 23 cases came out with positive results. Both Chi square test and Spearman’s rank correlation analysis Wntless expression had no correlation with Her-2 amplication status.Oncomine data mining analysis showed that Wntless mRNA levels in invasive ductal carcinoma were lower than those in normal and cancer adjcant tissues (P<0.05). Wntless mRNA levels in breast ductal carcinoma in situ, lobular carcinoma, mucinous carcinoma, medullary breast carcinoma and mixed lobular and ductal breastcarcinoma were also lower than those in normal tissues (P<0.05). Besides, Wntless mRNA levels in invasive ductal carcinoma of the breast were significantly lower than that in mixed ductal and breast cancer (P<0.05) and Wntless mRNA levels were significantly lower in the invasive breast cancer:basal-like type than those in the invasive breast cancer: Luminal type(P<0.05).Kaplan-Meier survival analysis indicated lower expression of Wntless was apt to recur approaching statistical significance (P=0.085) and was also associated with shorter survival (P< 0.05). Univariate survival analysis showed that menopausal status, histological grade, lymph node metastasis and clinical pathological staging, ER, PR and HER-2, Ki-67 and Wntless were significantly associated with patients’ disease free survival (P<0.05), and menopausal status, clinicpathological staging, lymph node metastasis, ER, PR, Ki-67 and Wntlesss were significantly associated with patients’ overall survival (P<0.05).Multivariate survival analysis showed that menopausal status, lymph node metastasis, ER, PR, and Wntless were independent prognostic factors associated with patients’ disease free survival (P< 0.05), and menopausal status, lymph node metastasis, ER and Wntless were independent prognostic factors associated with patients’ overall survival (P< 0.05).Conclusions:(1) The expression of Wntless in IDC-NOS tissue increases significantly higher than those in normal breast tissues, which indicated that it plays an important role in the occurrence and development of IDC-NOS and malignant transformation. However, the relevant mechanism remained unclear and more insights was still needed to further analyze the mechanism of Wntless in IDC-NOS.(2) Wntless is negatively related with ER expression in IDC-NOS, while it is not so significant with PR, Her-2, Ki-67 expression and clinical parameters.(3) Wntless may be closely related with tumor occurrence, development and prognosis of IDC-NOS and higher expression may indicate better prognosis and lower recurrence risk. Thus, Wntless could be used as an potential indicator of better prognosis of IDC-NOS.