HISTOLOGY AND HISTOPATHOLOGY

From Cell Biology to Tissue Engineering

 

Immunohistochemical expression profiles of mucin antigens in salivary gland mucoepidermoid carcinoma: MUC4- and MUC6-negative expression predicts a shortened survival in the early postoperative phase

Kie Honjo1,2, Tsubasa Hiraki1, Michiyo Higashi1, Hirotsugu Noguchi3, Mitsuharu Nomoto4, Takuya Yoshimura1,2, Surinder K. Batra5,6, Suguru Yonezawa1, Ichiro Semba7, Norifumi Nakamura2, Akihide Tanimoto1 and Sohsuke Yamada1,8

Departments of 1Pathology, Field of Oncology, 2Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 3Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 4Department of Pathology, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan, 5Department of Biochemistry and Molecular Biology and 6Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA, 7Division of Oral Pathology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, and 8Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan
K. Honjo and S. Yamada contributed equally to this study

Offprint requests to: Sohsuke Yamada, M.D., Ph.D., Department of Pathology and Laboratory Medicine, Kanazawa Medical University, 1-1 Uchinada, Ishikawa, 920-0293, Japan. e-mail: sohsuke@kanazawa-med.ac.jp


Summary. In mucoepidermoid carcinoma (MEC), the most common salivary gland carcinoma, there is a lack of novel prognostic markers, but post-operative early recurrence strongly affects the clinical course and a poor outcome. It is critical to predict which MEC patients are prone to develop recurrence/metastases. Mucins play pivotal roles in influencing cancer biology, thus affecting cell differentiation, adhesion, carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to elucidate the significance of expression profiles for mucins, particularly MUC4 and MUC6, and their correlations with various clinicopathological features and recurrence in salivary gland MECs. We performed immunohistochemical analyses on patients with surgically resected primary MEC using antibodies against mucin core proteins MUC4/8G7 and MUC6/CLH5 in 73 paraffin-embedded samples. Recurrence was noted in 15 of 73 (20.5%) patients. MUC4 or MUC6 expression was considered to be negative when <30% or 0% of the MEC cells showed positive staining, respectively. MUC4- and/or MUC6-negative expression respectively and variably showed a significant relationship to pathological tumor high-grade, the presence of lymphovascular invasion, lymph node metastasis and/or tumor-related death. In addition, MUC4 showed significantly negative co-expression with MUC6. Kaplan-Meier analyses revealed that not only single MUC4/6-negative expression but also the combination of both predicted significantly shorter disease-free and disease-specific survivals in MECs, especially within the first two years postoperatively. Therefore, each mucin plays a pivotal role in the pathogenesis of MEC progression. The detection of MUC4 and/or MUC6 might be a powerful parameter in the clinical management of MECs in the early postsurgical phase. Histol Histopathol 33, 201-213 (2018)

Key words: Mucoepidermoid carcinoma (MEC), Immunohistochemistry, MUC4, MUC6, Disease-free survival (DFS), Disease-specific survival (DSS)

DOI: 10.14670/HH-11-913