CAJ | 학술논문

背景与目的:随着化疗药物在肿瘤临床治疗中的广泛应用,肿瘤对化疗药物产生多药耐药性的问题越来越突出,已成为肿瘤联合化疗失败的主要原因之一.本研究检测β-catenin以及肿瘤耐药相关蛋白MRP2、P-gp、Bcl-2在食管鳞状细胞癌(esophageal squamoua cell carcinoma,ESCC)中的表达,探讨它们在ESCC的多药耐药发生发展中的作用和相互关系.方法:运用组织芯片技术、免疫组织化学方法以及图像分析技术检测582例ESCC及其癌旁294例正常黏膜、92例单纯细胞增生和87例不典型增生上皮组成的组织芯片中MRP2、P-gP、β-catenin及Bcl-2的表达情况,并分析其与各临床病理参数之间的关系.结果:MRP2、Bcl-2在ESCC中的累积光密度(integral optical density,IOD)值[分别为(195.7±175.9)×103和(90.5±112.5)×10~3]显著高于其在癌旁正常组织中的IOD值[分别为(104.8±86.1)×10~3和(25.2±46.6)×10~3],差异有统计学意义(P＜0.01);Pgp、β-catenin在ESCC中的IOD值[分别为(57.7±75.5)×10~3和(32.0±47.0)×10~3]显著低于其在癌旁正常组织中的IOD值[分别为(114.8±106.6)×10~3和(46.1±35.7)×10~3],差异有统计学意义(P＜0.01);随着ESCC的分化程度按高分化-中分化-低分化顺序依次改变,MRP2的IOD值依次递增,β-catenin在低分化ESCC中的IOD值大于其在中、高分化ESCC中的IOD值,Bcl-2在高分化ESCC中的IOD值低于其在中、低分化ESCC中的IOD值,差异有统计学意义(P＜0.01);β-catenin、Bcl-2在ESCC浸润至黏膜层的病例的癌组织标本中的IOD值大于其在ESCC浸润至肌层或浆膜层的病例的癌组织标本中的IOD值,差异有统计学意义(P＜0.01);有淋巴结转移的Bcl-2的IOD值显著高于无淋巴结转移(P＜0.01);ESCC中P-gp的表达分别与MRP2、Bcl-2的表达呈明显正相关(r=0.288和r=0.253,P＜0.01).结论:P-gp与MRP2及Bcl-2可作为ESCC多药耐药的预测因子.β-catenin可能在ESCC的发生发展中起着重要作用. 揹景與目的:隨著化療藥物在腫瘤臨床治療中的廣汎應用,腫瘤對化療藥物產生多藥耐藥性的問題越來越突齣,已成為腫瘤聯閤化療失敗的主要原因之一.本研究檢測β-catenin以及腫瘤耐藥相關蛋白MRP2、P-gp、Bcl-2在食管鱗狀細胞癌(esophageal squamoua cell carcinoma,ESCC)中的錶達,探討它們在ESCC的多藥耐藥髮生髮展中的作用和相互關繫.方法:運用組織芯片技術、免疫組織化學方法以及圖像分析技術檢測582例ESCC及其癌徬294例正常黏膜、92例單純細胞增生和87例不典型增生上皮組成的組織芯片中MRP2、P-gP、β-catenin及Bcl-2的錶達情況,併分析其與各臨床病理參數之間的關繫.結果:MRP2、Bcl-2在ESCC中的纍積光密度(integral optical density,IOD)值[分彆為(195.7±175.9)×103和(90.5±112.5)×10~3]顯著高于其在癌徬正常組織中的IOD值[分彆為(104.8±86.1)×10~3和(25.2±46.6)×10~3],差異有統計學意義(P＜0.01);Pgp、β-catenin在ESCC中的IOD值[分彆為(57.7±75.5)×10~3和(32.0±47.0)×10~3]顯著低于其在癌徬正常組織中的IOD值[分彆為(114.8±106.6)×10~3和(46.1±35.7)×10~3],差異有統計學意義(P＜0.01);隨著ESCC的分化程度按高分化-中分化-低分化順序依次改變,MRP2的IOD值依次遞增,β-catenin在低分化ESCC中的IOD值大于其在中、高分化ESCC中的IOD值,Bcl-2在高分化ESCC中的IOD值低于其在中、低分化ESCC中的IOD值,差異有統計學意義(P＜0.01);β-catenin、Bcl-2在ESCC浸潤至黏膜層的病例的癌組織標本中的IOD值大于其在ESCC浸潤至肌層或漿膜層的病例的癌組織標本中的IOD值,差異有統計學意義(P＜0.01);有淋巴結轉移的Bcl-2的IOD值顯著高于無淋巴結轉移(P＜0.01);ESCC中P-gp的錶達分彆與MRP2、Bcl-2的錶達呈明顯正相關(r=0.288和r=0.253,P＜0.01).結論:P-gp與MRP2及Bcl-2可作為ESCC多藥耐藥的預測因子.β-catenin可能在ESCC的髮生髮展中起著重要作用.
배경여목적:수착화료약물재종류림상치료중적엄범응용,종류대화료약물산생다약내약성적문제월래월돌출,이성위종류연합화료실패적주요원인지일.본연구검측β-catenin이급종류내약상관단백MRP2、P-gp、Bcl-2재식관린상세포암(esophageal squamoua cell carcinoma,ESCC)중적표체,탐토타문재ESCC적다약내약발생발전중적작용화상호관계.방법:운용조직심편기술、면역조직화학방법이급도상분석기술검측582례ESCC급기암방294례정상점막、92례단순세포증생화87례불전형증생상피조성적조직심편중MRP2、P-gP、β-catenin급Bcl-2적표체정황,병분석기여각림상병리삼수지간적관계.결과:MRP2、Bcl-2재ESCC중적루적광밀도(integral optical density,IOD)치[분별위(195.7±175.9)×103화(90.5±112.5)×10~3]현저고우기재암방정상조직중적IOD치[분별위(104.8±86.1)×10~3화(25.2±46.6)×10~3],차이유통계학의의(P＜0.01);Pgp、β-catenin재ESCC중적IOD치[분별위(57.7±75.5)×10~3화(32.0±47.0)×10~3]현저저우기재암방정상조직중적IOD치[분별위(114.8±106.6)×10~3화(46.1±35.7)×10~3],차이유통계학의의(P＜0.01);수착ESCC적분화정도안고분화-중분화-저분화순서의차개변,MRP2적IOD치의차체증,β-catenin재저분화ESCC중적IOD치대우기재중、고분화ESCC중적IOD치,Bcl-2재고분화ESCC중적IOD치저우기재중、저분화ESCC중적IOD치,차이유통계학의의(P＜0.01);β-catenin、Bcl-2재ESCC침윤지점막층적병례적암조직표본중적IOD치대우기재ESCC침윤지기층혹장막층적병례적암조직표본중적IOD치,차이유통계학의의(P＜0.01);유림파결전이적Bcl-2적IOD치현저고우무림파결전이(P＜0.01);ESCC중P-gp적표체분별여MRP2、Bcl-2적표체정명현정상관(r=0.288화r=0.253,P＜0.01).결론:P-gp여MRP2급Bcl-2가작위ESCC다약내약적예측인자.β-catenin가능재ESCC적발생발전중기착중요작용.
Background and Objective:As chemotherapy is generally used in the clinical treatment of cancer,the problem of multidrug resistance(MDR)of tumors against the chemotherapeutic agents becomes more and more serious.It has been the major cause for the failure of the chemotherapy.We detected the expressions of β-catenin and tumor drug resistance related proteins,MRP2,P-gp,and Bcl-2,in esophageal squamous cell carcinoma (ESCC)to explore their function and correlation in the occurrence and development of MDR in ESCC.Methods:We used the tissue microarray technique,immunohistochemistry,and image analysis methods to detect the expressions of MRP2,P-gp,β-catenin,and Bcl-2 proteins and analyze their relationships with clinical data in a ESCC tissue microarray consisting of 582 specimens of ESCC,294 specimens of normal mucosa,92 specimens of basal cell hyperplasia,and 87 specimens of dysplasia adjacent to cancer tissue.Results:The integral optical density(IOD)of MRP2 and Bcl-2,which was 195.7±175.9(×10~3)and 90.5±112.5(×10~3),respectively,was significantly higher in ESCC than in normal mucosa.which was 1 04.8±86.1(×10~3)and 25.2±46.6(×10~3),respectively(P＜0.01).The IOD of P-gp and β-catenin,which was 57.7±75.5(×10~3)and 32.0±47.0(×10~3)respectively,was significantly lower in ESCC than in normal mucosa,which was 114.8±106.6(×10~3)and 46.1±35.7(×10~3),respectively(P＜0.01).According to the following order.well differentiated-moderately differentiated-poorly differentiated.the 1OD of M RP2 increased in ESCC(P＜0.01).The IOD of β-catenin was higher in poorly differentiated ESCC than in well or moderately differentiated ESCC(P＜0.01).The IOD of Bcl-2 was lower in well differentiated ESCC than in poorly and moderately differentiated ESCC(P＜0.01).The IOD of β-catenin and Bcl-2 was higher in the ESCC of specimens with infiltration depths that were in membrane mucosa than those in the muscular layer or serous coat(P＜0.01).The IOD of Bcl-2 was significantly higher in cases with Iymph node metastasis than in cases without (P＜0.01).Positive correlations which were respectively between the expressions of P-gp and MRP2,the expressions of P-gp and Bcl-2 were found(r=0.288 and r=0.253.respectively,P＜0.01).Conclusions:MRP2,P-gp,and Bcl-2 may be taken as prognostic factors for MDR of ESCC.β-catenin may play an important role in carcinogenesis and progression of ESCC.