CAJ | 학술논문

背景与目的：食管癌术后辅助化疗主要针对淋巴结转移灶，但转移灶中肿瘤细胞群多药耐药(multidrug resistance，MDR)的异质性是影响化疗效果的一个主要因素。目前有关食管鳞癌MDR的研究多限于肿瘤原发灶，其原发灶与淋巴结转移灶MDR是否存在异质性鲜见报道。本研究探讨MDR相关蛋白在食管鳞癌原发灶与淋巴结转移灶中的差异表达及意义。方法：对54例食管胸段鳞癌原发灶及相应淋巴结转移灶分别进行MDR相关蛋白肺耐药相关蛋白(LRP)、P-糖蛋白(P-gp)、拓扑异构酶Ⅱ(TOPO-Ⅱ)、胸甘酸合成酶(TS)、谷胱甘肽-S-转移酶(GST-π)免疫组织化学染色，比较同一患者MDR相关蛋白在肿瘤原发灶和淋巴结转移灶中表达和耐药的差异，分析其与组织分化程度的关系。结果：肿瘤原发灶与淋巴结转移灶LRP、P-gp、TS、TOPO-Ⅱ、GST-π表达和耐药不一致率分别为63.0%和26.9%、42.6%和22.2%、48.1%和25.9%、50.0%和29.6%、18.5%和1.9%。LRP在原发灶与淋巴结转移灶的表达差异有统计学意义(P=0.026)，其余4种蛋白在原发灶与淋巴结转移灶的表达没有差异，GST-π在原发灶与淋巴结转移灶中均表达。MDR相关蛋白表达与组织分化程度无关。结论：食管鳞癌原发灶与淋巴结转移灶存在MDR的异质性现象。对淋巴结转移灶检测MDR相关蛋白表达水平有助于指导食管鳞癌术后选择合理的化疗方案。
배경여목적：식관암술후보조화료주요침대림파결전이조，단전이조중종류세포군다약내약(multidrug resistance，MDR)적이질성시영향화료효과적일개주요인소。목전유관식관린암MDR적연구다한우종류원발조，기원발조여림파결전이조MDR시부존재이질성선견보도。본연구탐토MDR상관단백재식관린암원발조여림파결전이조중적차이표체급의의。방법：대54례식관흉단린암원발조급상응림파결전이조분별진행MDR상관단백폐내약상관단백(LRP)、P-당단백(P-gp)、탁복이구매Ⅱ(TOPO-Ⅱ)、흉감산합성매(TS)、곡광감태-S-전이매(GST-π)면역조직화학염색，비교동일환자MDR상관단백재종류원발조화림파결전이조중표체화내약적차이，분석기여조직분화정도적관계。결과：종류원발조여림파결전이조LRP、P-gp、TS、TOPO-Ⅱ、GST-π표체화내약불일치솔분별위63.0%화26.9%、42.6%화22.2%、48.1%화25.9%、50.0%화29.6%、18.5%화1.9%。LRP재원발조여림파결전이조적표체차이유통계학의의(P=0.026)，기여4충단백재원발조여림파결전이조적표체몰유차이，GST-π재원발조여림파결전이조중균표체。MDR상관단백표체여조직분화정도무관。결론：식관린암원발조여림파결전이조존재MDR적이질성현상。대림파결전이조검측MDR상관단백표체수평유조우지도식관린암술후선택합리적화료방안。
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.