Background: The epithelial cell adhesion molecule (EpCAM) has been reported its various roles in variety of cancers, particularly in adenocarcinoma. EpCAM broad expression on human carcinomas and its involvement in cell proliferation have brought EpCAM into focus as an immunotherapeutic target for therapeutic strategies. However, its expression level and role in esophageal squamous cell carcinoma (ESCC) is remained unclear. This study is to investigate the clinicopathologic significance of EpCAM expression in ESCC.
Methods: The EpCAM expression was immunohistochemically investigated in 74 primary ESCCs with R0 resection without any preoperative treatment using the monoclonal antibody. We evaluated the intensity of the stain in 4 grades. We considered 3 (strong) and 2 (medium) as “positive” and 1 (weak) and 0 (negative) as “negative”. Down regulation of EpCAM gene expression was performed using the shRNA in EpCAM high ESCC cell line (TE4-shRNA), TE4. The cell proliferation assay was performed using cell counting kit to assess cell proliferation in vitro. To evaluate cell proliferation and tumorgenesis in vivo, we inoculated TE4 and TE4-shRNA into nude mice subcutaneously. The size and incidence of subcutaneous tumors were recorded.
Results: Thirty-six (48.6%) patients showed positive for EpCAM immunostaining and 38 (51.4%) patients showed negative. EpCAM expression was not significantly correlated with histology, tumor depth, regional lymph node metastasis, disease stage, lymphatic invasion, or venous invasion. However, high expression of EpCAM was significantly associated with poor survival in ESCC patients (P = 0.026). Multivariate Cox regression analysis showed overexpression of EpCAM was a significant and independent prognostic factor for surgically treated ESCC (P = 0.004). The cell proliferation rate of TE4-shRNA was lower than TE4 in vitro. TE4 cells could initiate tumors in 7 of 10 injected nude mice, whereas TE4-shRNA cells produced only 2 of 10 injected mice at 6 weeks after transplantation. The tumor sizes were larger in the TE4 cells than in the TE4-shRNA cells.
Conclusion: High expression of EpCAM was independent prognostic factor for surgically treated ESCC. EpCAM expression level could change cell proliferation and tumorgenesis in vitro and in vivo. These results suggested that EpCAM might be a potential molecular target for esophageal cancer therapy.
Citation Format: Tatsuo Matsuda, Hiroya Takeuchi, Sachiko Matsuda, Kunihiko Hiraiwa, Hirofumi Kawakubo, Rieko Nakamura, Tsunehiro Takahashi, Norihito Wada, Yoshiro Saikawa, Tai Ohmori, Yuko Kitagawa. The role of EpCAM expression in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3992. doi:10.1158/1538-7445.AM2013-3992