Possible correlation of apical localization of MUC1 glycoprotein with luminal A-like status of breast cancer

Abstract

Abstract Adjuvant chemotherapy has played a major role in the treatment of hormone receptor-positive breast cancer for many years. To better determine which patient subsets need adjuvant chemotherapy, various gene expression analyses have been developed, but cost-effective tools to identify such patients remain elusive. In the present report, we retrospectively investigated immunohistochemical expression and subcellular localization of MUC1 in primary tumors and examined their relationship to tumor malignancy, chemotherapy effect and patient outcomes. We retrospectively examined three patient cohorts with hormone receptor-positive/human epidermal growth factor receptor 2-negative invasive breast cancer: 51 patients who underwent 21-gene expression analysis (multi-gene assay-cohort), 96 patients who received neoadjuvant chemotherapy (neoadjuvant chemotherapy-cohort), and 609 patients whose tumor tissue was used in tissue-microarrays (tissue-microarray-cohort). The immunohistochemical staining pattern of the anti-MUC1 monoclonal antibody, Ma695, was examined in cancer tissues, and subcellular localization was determined as apical, cytoplasmic or negative. In the multi-gene assay-cohort, tumors with apical patterns had the lowest recurrence scores, reflecting lower tumor malignancy, and were significantly lower than MUC1-negative tumors (P = 0.038). In the neoadjuvant chemotherapy-cohort, there was no correlation between MUC1 staining patterns and effects of chemotherapy. Finally, in the tissue-microarray-cohort, we found that patients with apical MUC1 staining patterns had significantly longer disease-free-survival and overall survival than other patterns (P = 0.020 and 0.039, respectively). Our data suggest that an apical MUC1 staining pattern indicates luminal A-likeness. Assessment of the subcellular localization of MUC1 glycoprotein may be useful for identifying patients who can avoid adjuvant chemotherapy.