Expression of MUC4 is Correlated With Chemoresistance and Survival in Oral Squamous Cell Carcinoma

MUC4 mucin is now known to be expressed in various normal and cancer tissues, and is independent indicators of worse prognosis in many human epithelial cancers [1,2]. Recently, it has been reported that MUC4 can play critical roles for chemoresistance [3-6]. We have previously reported that MUC4 expression in cancer cells correlates with tumor aggressiveness, local recurrence and subsequent nodal metastasis after first therapy, and that survival rate is significantly worse in patients with MUC4 expression compared to those with no MUC4 expression in oral squamous cell carcinoma (OSCC) [7], however, its correlation with chemoresistance in OSCC is still unknown. The purpose of the present study was to investigate the possible association between MUC4 expression and effectiveness of chemotherapy in the patients with OSCC. This study included 84 patients who treated with chemotherapy and surgical resection for primary oral cancer at the Department of Oral Surgery at Kagoshima University Hospital in Kagoshima, Japan between 1992 and 2008. The present study was approved by the Human Ethics Committee of Kagoshima University Graduate School of Medical and Dental Sciences. MUC4 expression was determined using immunohistochemistry in 35 patients who received 5-fluorouracil and 49 patients who received platinum-based anticancer drugs. Its prognostic significance in each group or whole patient was statistically analyzed on the basis of detailed clinicopathologic factors. The histopathological effect of chemotherapy was evaluated according to Oboshi-Shimosato classification. In both groups (5-Fu group and platinum-based anticancer drugs group), the frequency of tumors with chemoresistance was significantly high in patients with MUC4 positivity compared to those with MUC4 negativity, respectively (p=0.010 and 0.011, chi-square test). The Kaplan–Meier analysis of whole patient showed that MUC4 positive patients had relatively lower disease-free survival rates than those without MUC4 expression (p=0.24, log-rank test). Our finding suggests that MUC4 is a potential molecular marker for predicting effectiveness of perioperative chemotherapy, and that the MUC4 down-regulation may constitute a potential therapeutic strategy for improving the efficacy of anticancer drugs in the patients with OSCC.

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