Study Of Correlation Between Microtubule-Associated Protein 1 Light Chain 3 And Prognosis Of ESCC

Esophageal carcinoma is the eighth most common cancer and the sixth leading cause of cancer death in the world. The distribution of esophageal cancer is heterogenous. Esophageal squamous cell carcinoma (ESCC) continues to be the major type(more than 90%) of esophageal cancer in Asia, in contrast, esophageal adenocarcinoma predominately affects the whites. The prognostic factors of ESCC include tumor location, depth of tumor invasion, number of involved lymph nodes, histological grade, pTNM stage and cTNM stage.Microtubule-associated protein light chain 3 (LC-3) is a key mediator bridging autophagy, apoptosis and differentiation. However, its role and clinical significance in resectable esophageal squamous cell carcinoma (ESCC) is still scanty. The purpose of this study was to investigate the clinical significance of LC-3 by immunohistochemistry in a group of patients with ESCC, which treated with surgical resection and concurrent radiochemotherapy respectively. The study was divided into two parts.Part 1Objective:Microtubule-associated protein light chain 3 (LC-3) is a key mediator bridging autophagy, apoptosis and differentiation. However, its role and clinical significance in resectable esophageal squamous cell carcinoma (ESCC) is still scanty. The purpose of this study was to investigate the clinical significance of LC-3 by immunohistochemistry in a group of patients with ESCC treated with surgical resection.Methods:Tissue microarray that included 253 surgically resected ESCC specimens was successfully generated for immunohistochemical evaluation. The clinical/prognostic significance of LC-3 expression was analyzed statistically. The association of LC-3 expression with the ESCC survival rate was assessed by Kaplan-Meier and Cox proportional-hazards regression.Results:The results showed that the immunostaining of LC-3 was distributed in cytoplasm and plasma-membrane. Significantly high LC-3 expression was found in ESCC cells compared with that of normal esophageal epithelial cells. Patients with low expression of LC-3 demonstrated higher overall survival compared with those with high expression of LC-3 (mean of 71.1 months versus 55.5 months, P= 0.022). A similar result was observed for disease-free survival (mean of 68.7 months versus 51.8 months, P= 0.021). In subgroup analysis, LC-3 expression could stratify pN0 patients with ESCC. Multivariate analysis showed that the level of LC-3 expression was an independent prognostic factor in ESCC (RR= 1.407, P= 0.049). Conclusion:This study shows high level of LC-3 suggests poor prognosis for resectable ESCC patients.Part 2Objective:To study the relationship between microtubule-associated protein 1 light chain 3 (LC-3) and the clinicopathologic characteristics and prognosis of patients with esophageal squamous cell carcinoma(ESCC) that received concurrent chemo-radiotherapy(CRT).Method:The clinicopathologic and follow-up data of 93 patients with ESCC were analyzed retrospectively.The expression of LC-3 in 93 cases of ESCC tissues before treatment was detected by immunohistochemistry(IHC).The relationship between LC-3 expression and clinicopathologic factors was examined. The survival analysis was performed to find independent prognosis factors.Results:The results showed that the immunostaining of LC-3 was distributed in cytoplasm. LC-3 expressed in cytoplasm was not correlated with all clinicopathologic factors, including tumor length, location, differentiation, T-stage,N-stage, M-stage(P>0.05).Patients with low expression of LC-3 demonstrated the similar overall survival compared with those with high expression of LC-3 (mean of 42.2 months versus 30.0 months, P>0.05). In subgroup analysis, LC-3 expression could not stratify cNl patients with ESCC.Survival analysis demonstrated that LC-3 was not correlated with the prognosis of patients with ESCC who received CRT.Conclusion:LC-3 is not a prognostic factor for ESCC who were unresectable, and the detection of LC-3 by IHC is of minor value for revaluating prognosis of patients with ESCC who receive CRT.Conclusion of the study:The results showed that the immunostaining of LC-3 was distributed in cytoplasm,the level of LC-3 expression was an independent prognostic factor in ESCC who underwent surgery, but LC-3 is not a prognostic factor for ESCC who underwent concurrent radiochemotherapy.