P1.17-002 Clinicopathological Significance of Epithelial Mesenchymal Transition in Thymic Cancer

Abstract

The epithelial to mesenchymal transition (EMT) is a fundamental biological process during which epithelial cells change to a mesenchymal phenotype which has a profound impact on cancer progression. It has been proposed that increased expressions of EMT markers, loss of epithelial markers such as E-cadherin, and altered expressions of mesenchymal markers such as N-cadherin are called as cadherin switching and associated with poor prognosis in cancer case. We analyzed the expression of E-cadherin and N-cadherin in thymic cancer to determine the relationship to clinicopthological factors and prognosis. We collected the data of 31 patients with thymic cancer from our institution between 2000 and 2014. Immunohistochemistry was used to examine the expression of EMT markers, E-cadherin and N-cadherin in tumor specimens. We evaluated the correlation between EMT and prognosis in patients with thymic cancer. We also compared expressions of the cadherins in tumor specimens obtained both before and after preoperative chemoradiotherapy or chemotherapy from 14 patients with thymic cancer who underwent preoperative biopsy in our hospital. Eighteen patients underwent preoperative treatment. The resection was extended to the surrounding organs in addition to thymectomy including thymic tumor and anterior mediastinal lymphadenectomy. Twenty-six patients had a R0 resection. Pathological findings revealed that one patient had Masaoka stage I disease, one had II, 20 had III, one had IVa, and 8 had IVb. The histological diagnosis was squamous cell carcinoma in 24, undifferentiated carcinoma in 4, and others in 3 patients. Immunohistochemically, decreased expression of E-cadherin or upregulation of N-cadherin was detected in surgically resected specimens in 15 patients whose tumor was classified as EMT marker-positive. According to a clinicopathological comparison of these groups, EMT status was not related to preoperative therapy, Masaoka staging, or histology. The 5-year survival rate for all patients was 86%, 63% for EMT marker-positive, and 100% for EMT marker-negative. The survival rate of patients with EMT marker-positive tumors was significantly lower than that of those with EMT marker-negative tumors. Decreased expression of E-cadherin or upregulation of N-cadheirn was detected in surgically resected specimens after preoperative treatment compared with biopsy specimens obtained before treatment in 10 of 14 patients. EMT marker expression such as cadherin switching was detected in thymic cancer tumor and was more often detected after preoperative treatment, indicating that EMT may affect the degree of malignant potential in thymic cancer and make them insensitive to treatment.