Abstract 4689: The alterations and significance of hMLH1 and TGFβII receptor expression during esophageal carcinogenesis.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Esophageal cancer is one of the most common cancers in the world, prognosis is very poor and five-year survival time is less than 20%. Epidemiology studies have revealed a strong association between cancer risks and genetic-environmental factors, the underlying mechanisms are largely unknown. Previous studies have also demonstrated that activation of oncogene and inactivation of tumor suppressor genes contribute to disruption of esophageal epithelial cell maturation, leading to tumor formation. Most recently, a group of DNA mismatch repair (MMR) genes, such as hMSH2,hMSH6,hMLH1, attracts attention, because their aberrant expression significantly affects tumor formation, as well demented in colorectal, gastric and endometrial cancers. But the alteration in esophageal carcinogenesis has not been reported. The present study was to determine the alteration of hMLH1 and its potential target TGFβII receptor (TGFβIIR) and the significance in esophageal carcinogenesis. Materials and methods: 108 esophageal tissues including 20 normal esophageal mucosa (NE), 21 dysplasia (DYS), 25 cancer in situ (CIU) and 42 squamous cell carcinoma (SCC), were collected. All patients did not accept chemotherapy or radiotherapy before surgical operation. Immunohistochemical staining was used to determine the expression of hMLH1 and TGFβIIR in NE, DYS, CIU and SCC, using anti-human hMLH1 and TGFβIIR antibodies. The expression was scored using semi-quantification system. The correlation between protein expression and clinical characteristics was analyzed. Results: 95% (19/20) of NE showed hMLH1 nuclear expression, but the express of hMLH1 was reduced in DYS (71%, 15/21) and CIU (68%, 17/25), and it was dramatically reduced to 15% (6/42) in SCC (p<0.05). Altered expression of hMLH1 was also negatively associated with SCC differentiation (40% in well differentiated SCC, 10% in moderate differentiated SCC and no expression at poorly differentiated SCC, p<0.05), but was not associated with the status of metastasis, depth of invasion, gender and ages. Similar pattern of TGFβRII was seen in esophageal tissues: about 10% SCC expressed cytoplastic TGFβRII, but 62%DYS, 64% CIU and 85% NE expressed TGFβRII. The difference was significant (p<0.05). Like hMLH1, TGFβRII expression was not associated with metastasis, invasion, gender and ages. Unlike hMLH1, TGFβRII expression was not associated with SCC differentiation. More interestingly, the altered expression of hMLH1 was well correlated with alteration of TGFβRII (r=0.563, p<0.05). Conclusion: Both hMLH1 and TGFβRII expression were significantly reduced during esophageal carcinogenesis. But whether the reduced expression of hMLH1 and TGFβRII could be a biomarker for cancer detection or risk prediction, and whether there is a regulatory interaction between these two proteins during carcinogenesis, is not clear and needs further investigation. Citation Format: Yunjuan Jiao, Weixing Zhao, Xin Dong, Xiaoyu Yang, Zheying Zhang, Yongxia Wang, Jing Cui, Zhiqiang Qin, Wancai Yang, Wancai Yang. The alterations and significance of hMLH1 and TGFβII receptor expression during esophageal carcinogenesis. [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 4689. doi:10.1158/1538-7445.AM2013-4689 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.