Expression Of Mucins (MUC1, MUC2, MUC5AC And MUC6)and Their Significance In Invasive Ductal Breast Carcinoma

[Objective] Mucins (MUCs) are a large family of glycoproteins expressed by many kinds of epithelial cells. It has been found that mucins play important roles in the development of breast cancer, and have potential roles as a molecular therapeutic target. Now mucins have become a hot topic in current breast cancer research. MUC1is the most studied mucin member; while the other mucin members are less studied compare to MUC1. And the conclusions of these studies are inconsistent. In this study, the expression of several mucins (MUC1, MUC2, MUC5AC and MUC6) in invasive breast ductal carcinoma has been evaluated. And the biologic and clinicopathologic significance of these mucins in invasive breast ductal carcinoma also has been analyzed.[Methods! Archival tissue blocks of240cases with invasive breast ductal carcinoma were continually collected. Tissue microarray and immunohistochemical methods were used to determine the expression of MUC1、MUC2、MUC5AC and MUC6. At the same time the clinicopathologic and follow-up information have been collected. The relationship between mucins expression and clinicopathologic features were analyzed using χ2test, SPSS19.0software.[Results](1) General characteristics:Among the240collected cases,207of them have integrated information in the end. All of the207cases are female, from23to70years old, and the average age is52.7year-old. There are grade Ⅰ7cases, grade Ⅱ135cases and grade Ⅲ65cases; tumor size≤2cm78cases,>2cm129cases; with lymph node metastasis125cases, without lymph node metastasis82cases; with recurrence or distant metastases50cases, without recurrence or distant metastases157cases during the follow-up time period of0.5-5years. Within the follow-up period,11cases dead from breast cancer recurrence or distant metastases, and6cases dead due to non-breast cancer reason.(2) Among the207case, MUC1expression was detected in185cases, and the positive rate is89.4%. Its expression was associated with lower histological grade (r=-0.17, P<0.05), estrogen receptor (ER) positive (r=0.17, P<0.05) and absence of lymph node (LN) metastasis (r=-0.15, P<0.05). It seems no correlation between MUC1expression level and age, tumor size, HER-2, recurrence or distant metastases.(3) Regarding MUC1subcellular localization,4.3%(8/185) in pure luminal/apical,21.6%(40/185) in luminal and cytoplasmic,74.1%(137/185) in cytoplasmic with circumferential membranous accentuation. MUC1expression in cytoplasmic with circumferential membranous accentuation was associated with recurrence or distant metastases (P<0.05).(4) MUC2expression was quite low, in only4.3%(9/207) of all the207cases. Because of the low expression rate, we did not analyze ir by statistic method.(5) MUC5AC was expressed in42.0%(87/207) of the cases. Among the clinicopathological variables, only lower grade (r=-0.239, P<0.05) as well as ER-positive (r=1.55, P<0.05) has been associated with MUC5AC expression.(6) MUC6was expressed in22.2%(46/207) of the cases. Apart from the associations between MUC6and HER-2positive (r=0.287,P<0.05), no other associations with any clinicopathological variables were found.[Conclusions](1) MUC1are expressed in the majority of the cases. Its expression was associated with lower histological grade, ER positive and absence of lymph node metastasis. Regarding MUC1subcellular localization, MUC1expression in cytoplasmic with circumferential membranous accentuation was associated with recurrence or distant metastases. Subcellular localization of MUC1suggested a potential prognostic value in postoperative recurrence and metastasis.(2) The expression rates of MUC2, MUC5AC, MUC6in invasive breast ductal carcinoma are4.3%,42.0%and22.2%respectively. MUC5AC associated with lower grade as well as ER-positive; and MUC6have association with HER-2positive. These need further study to be confirmed.