Gan Si-Yuan, Zhong Xue-Yun, Xie Si-Ming, Li Su-Mei, Peng Hui, Luo Feng
Department of Pathology, Medical College, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
Chin J Cancer. 2010 Mar;29(3):300-5. doi: 10.5732/cjc.009.10599.
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 beta-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.
We used the tissue microarray technique, immunohistochemistry, and image analysis methods to detect the expressions of MRP2, P-gp, beta-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.
The integral optical density (IOD) of MRP2 and Bcl-2, which was 195.7 +/- 175.9 x 10(3)) and 90.5 +/- 112.5 x 10(3)), respectively, was significantly higher in ESCC than in normal mucosa, which was 104.8 +/- 86.1 x103) and 25.2 +/- 46.6 x 10(3)), respectively (P < 0.01). The IOD of P-gp and beta-catenin, which was 57.7 +/- 75.5 x 10(3)) and 32.0 +/- 47.0 x 10(3)) respectively, was significantly lower in ESCC than in normal mucosa, which was 114.8 +/- 106.6 x 10(3)) and 46.1 +/- 35.7 x 10(3)), respectively (P < 0.01). According to the following order, well differentiated moderately differentiated poorly differentiated, the IOD of MRP2 increased in ESCC (P < 0.01). The IOD of beta-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 beta-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 lymph 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).
MRP2, P-gp, and Bcl-2 may be taken as prognostic factors for MDR of ESCC. beta-catenin may play an important role in carcinogenesis and progression of ESCC.
由于化疗在癌症临床治疗中普遍应用，肿瘤对化疗药物的多药耐药（MDR）问题日益严重，已成为化疗失败的主要原因。我们检测了食管鳞状细胞癌（ESCC）中β-连环蛋白及肿瘤耐药相关蛋白MRP2、P-糖蛋白（P-gp）和Bcl-2的表达，以探讨它们在ESCC多药耐药发生发展中的作用及相关性。
我们采用组织芯片技术、免疫组化和图像分析方法，检测了由582例ESCC标本、294例正常黏膜标本、92例基底细胞增生标本和87例癌旁不典型增生标本组成的ESCC组织芯片中MRP2、P-gp、β-连环蛋白和Bcl-2蛋白的表达，并分析它们与临床资料的关系。
ESCC中MRP2和Bcl-2的积分光密度（IOD）分别为（195.7±175.9）×10³和（90.5±112.5）×10³，显著高于正常黏膜中的（104.8±86.1）×10³和（25.2±46.6）×10³（P<0.01）。ESCC中P-gp和β-连环蛋白的IOD分别为（57.7±75.5）×10³和（32.0±47.0）×10³，显著低于正常黏膜中的（114.8±106.6）×10³和（46.1±35.7）×10³（P<0.01）。在ESCC中，按高分化、中分化、低分化顺序，MRP2的IOD升高（P<0.01）。低分化ESCC中β-连环蛋白的IOD高于高分化或中分化ESCC（P<0.01）。高分化ESCC中Bcl-2的IOD低于低分化和中分化ESCC（P<0.01）。浸润深度在黏膜层的ESCC标本中β-连环蛋白和Bcl-2的IOD高于肌层或浆膜层（P<0.01）。有淋巴结转移病例中Bcl-2的IOD显著高于无淋巴结转移病例（P<0.01）。发现P-gp与MRP2的表达、P-gp与Bcl-2的表达之间分别存在正相关（r分别为0.288和0.253，P<0.01）。
MRP2、P-gp和Bcl-2可能作为ESCC多药耐药的预后因素。β-连环蛋白可能在ESCC的发生发展中起重要作用。
