Activation of C-Jun N-Terminal Kinase Is Associated with Histological Grade of Mucoepidermoid Carcinoma
Hua Zhong, Angela Omilian, Carl Morrison, Bo Xu. Roswell Park Cancer Institute, Buffalo, NY
Background: Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the salivary gland. Previous studies demonstrate that CTRC1-MAML2 fusion transcript, resulting from t(11:19) translocation, is present in more than half of MECs. This translocation is associated with lower histologic grades and improved survival. In cultured cell lines, CTRC1 acts as a potent and indispensable modulator for activated protein 1 (AP1) transcriptional function which leads to anti-proliferation and pro-apoptosis. The intracellular signaling pathway mediating activation of AP1, however, has not been illustrated in human tissue of MEC. In this study, we investigate the activation of c-Jun N-terminal kinase (JNK) in human MEC by immunohistochemistry on sections of tissue microarray (TMA).
Design: Twenty-two cases of MECs, untreated before surgery, were identified at our institution from 2000 to 2010. There were 11 of major salivary gland origin and 11 of minor salivary gland origin. Tumors were graded as low, intermediate and high grade according to WHO criteria. Immunohistochemical studies were performed on sections of TMA by using a mouse monoclonal antibody against phosphorylated Thr 183 and Tyr 185 of JNK (pJNK) of human origin. Activation of JNK was determined by nuclear staining of pJNK. Scoring of immunostain intensity was based on our previously published method.
Results: Positive nuclear staining of pJNK was demonstrated in 12 out of 13 low grade (92.3%), 2 of 5 intermediate grade (40.0%) and 2 of 4 high grade (50.0%) tumors. In addition, the percentage of pJNK positive tumors was significantly higher in low grade MECs in comparison with those in intermediate and high grade tumors (Pearson's Chi-Square test, p = 0.013).
Conclusions: Activation of JNK is associated with tumor cell differentiation in MEC. These results explain previous findings that t(11:19) translocation resulting the fusion transcript of CTRC1-MAML2 is present in majority of low grade MECs. Our future studies will be directed to explore the correlation between t(11;19) translocation and activation of JNK in these MECs.
Category: Head & Neck
Monday, March 19, 2012 2:15 PM
Platform Session: Section F, Monday Afternoon