The heterogenous expression and signiifcance of multidrug resistance-associated proteins in primary tumors and metastatic lymph nodes in patients with esophageal squamous cell carcinoma / 中国癌症杂志

ABSTRACT

Background and purpose: Postoperative chemotherapy targets the metastatic cancer in the remaining lymph nodes, but the heterogeneity in multidrug resistance (MDR) of metastatic cancer cells is a main factor affecting chemotherapeutic efficacy. Recent studies only examined the primary lesion of esophageal squamous cell carcinoma(ESCC). There is no report about heterogeneity between the primary tumor and metastases lymph node. The purpose of this study was to explore the heterogenous expression and clinical signiifcance of multidrug resistance (MDR) associated proteins in primary tumors and metastatic lymph nodes in patients with thoracic ESCC. Methods:The expressions of lung cancer associated resistance protein (LRP), P-glycoprotein (P-gp), topoisomeraseⅡ(TOPO-Ⅱ), thymidylate synthase (TS), glutathione S-transferase-π (GST-π) were examined by immunohistochemistry in primary lesions and corresponding metastatic lymph nodes in 54 patients with thoracic ESCC. The differences between expression of primary lesions and matched metastatic lymph nodes were compared and analyzed in relationship with tissue differentiation degree. Results: The discordant rates of the expression and drug resistance between primary lesions and corresponding metastatic lymph nodes in LRP, P-gp, TS, TOPO-Ⅱ and GST-π were 63.0% and 26.9%, 42.6%and 22.2%, 48.1%and 25.9%, 50.0%and 29.6%, 18.5%and 1.9%respectively. The expression of LRP showed signiifcant difference between the primary tumors and lymph nodes (P=0.026). No signiifcant differences were found for the other four proteins, and GST-πwas expressed in all patients in both the primary tumors and lymph nodes. Protein expression was not associated with degree of differentiation. Conclusion:There is evident of heterogenous expression of MDR associated proteins in metastatic lymph nodes compared to the primary tumors of ESCC. The examination of expression levels of MDR associated proteins in metastatic lymph nodes is helpful to select the postoperative rational chemotherapy plan.