The Relationship Between Expression Of Mrp2, Mrp3 Protein And Clinical Pathological Features In Esophageal Squamous Cell Carcinoma

Esophageal carcinoma is the eighth of all the most common malignent cancers worldwide. Mortality is the sixth worldwide and fourth in china. There are about 300,000 people who die of esophageal carcinoma and 150,000 people in china which is about a quarter of the people who die of malignent carcinoma. Surgery is the principal treatment in the earlier period of esophageal carcinoma and combined therapy is the main treatment in the intermediate stage and advanced stage, Chemotherapy is one of the most important treatment. The binding of chemotherapy and radiation therapy can diminish the size of preoperative carcinoma or eliminate the relic postoperative carcinoma tissue. Chemotherapy is used in adjuvant therapy after surgical treatment, and the effect of single drug is very poor.Effect of combination chemotherapy is better than single durg. Whereas, status of chemotherapy has not be satisfied. Resistance to anti-cancer durgs is responsible for chemotherapy failure of tumors. Drug resistance to anti-cancer drugs includes nature resistance and acquired resistance, and consists of primary drug resistance(PDR) and multidrug resistance(MDR) on the basis of drug fast spectra. Primary drug resistance is defined that resistance is just to revulsive drug but cross resistance is not produced; Multidurg resistance is defined that tumor cells not only produce resistance to the chemotherapeutics after exposuring some chemotherapeutic for a long time, but also produce cross resistance to many specific drugs which have different structure and function with it. Multidurg resistance is the main reason for the failure of chemotherapy to cancers. The molecular mechanism that how tumor cells produce multidurg resistance is very complicated, ATP-binding cassette transport proteins-mediated multidurg resistance is the most capital and has been studied extensively in all the molecular mechanisms, and ABC proteins which have been studied extensively include P-glycoprotein (P-gp),multidrug-associated resistance protein 1(MRP1),breast carcinoma resistance protein(BCRP),lung resistance protein(LRP), they participate in the forming of many species of resistance by transmembrane transport, and the overexpressions of them lead to multidrug resistance. Esophageal carcinoma is one of the malignent cancers that are related to multidrug resistance. Studies have showed that P-gp,MRP1,BCRP and LRP may play very important roles in multidrug resistance of esophageal carcinoma. Recent research says that there have been other MRPs such as MRP2,MRP3 which participate in the occurrence of MDR, but there is fewer relative literature report about their expression in esophageal carcinoma tissues. By the method of immunohistochemistry, the expression of MRP2 and MRP3 were detected in esophageal carcinoma tissues and corresponding normal tissues. It was observed that expression of MRP2 and MRP3 (protein) correlated with pathological characteristics. The function of MRP2 and MRP3 and the correlation of them both in multidrug resistance and development of esophageal carcinoma could be further discussed and it would be useful to reverse their contribution on basis of intimate clinical data and the mechanism of multidrug resistance, thereby to elevate chemotherapeutic effect and judge prognosis of esophageal carcinoma, to extend the life span of patients with esophageal carcinoma.Materials and methods:68 patients with 44 males and 24 females who had undergone esophagectomy in department of Pathology, First Affiliated Hospital of Zhengzhou university in 2007, were enrolled in this study. The range of ages were 34～75 years.The average ages were 60.60±10.36 years. Esophageal squamous cell carcinoma had been confirmed by histopathological diagnosis in all tissue samples, 30 well-differentiated and 38 moderately and poorly differentiated; 44 below deep muscular layer and 24 above deep muscular layer; 26 with lymph node metastasis and 42 without lymph node metastasis. All patients had not received radiation therapy and/or chemotherapy before sugrical treatment. All tumor samples were fixed with 10% formalin and embeded with paraffin. Each block was sectioned serially at 4μm, one was stained with hematoxylin and erosin for histopathological analysis by two pathologists and the others were used for immunostaining. Blades were removaled endogenous hydrogen peroxidase with liquor hydrogenii dioxidi whose concentration was 3% after deparaffinage and hydration, recoverying antigen with microwave, then progressing the rest procedures according to the instruction of kit, the dilutions of antibodies both were 1: 100. To do positive control with positive blade and negative control with phosphate buffered solution(PBS). The datas were analysed by statistical software SPSS 10.0: Chi-squared test and Spearman's rank correlation were performed to compare difference bewteen groups and relativity analysis respectively. The significant difference was considered when the P value was less than 0.05.Results1. MRP2 and MRP3 express mainly in cell membrane and cytoplasm of cancer cells.2. The expressions of MRP2 protein which was 72.1% in carcinoma tissues were higher significantly than those in normal tissues which was 40.0%(P=0.003).It was not observed that MRP2 expressions were related to the depth of carcinoma tissue infiltration and lymph node metastasis(P>0.05). The expressions of MRP2 in well-differentiated group (86.7%) were significantly higher than those in moderately and poorly differentiated group(60.5%)(P=0.028).3. The expressions of MRP3 protein which was 67.6% in carcinoma tissues were higher significantly than those in normal tissues which was 36.7%(P=0.007). It was not observed that MRP3 expressions were related to the depth of carcinoma tissue infiltration and lymph node metastasis(P>0.05).The expressions of MRP3 in well-differentiated group (83.3%) were significantly higher than those in moderately and poorly differentiated group(55.3%)(P=0.019).4. It was significantly dependent between expressions of MRP2 and MRP3 in esophageal squamous cell carcinoma tissues(P=0.000).Conclusions:1. The expressions of MRP2 and MRP3 are higher in carcinoma tissues than those in normal tissues. It is indicated that the higher expression of MRP2 and MRP3 is related to the primary multidrug resistance in esophageal squmaous cell carcinoma.2. It is indicated that the overexpressions of MRP2 and MRP3 may involve in esophagus carcinogenesis, progression and the formation of metastasis. Both of their expressions are related to differentiation degree of esophageal squmaous cell careinoma tissues, so MRP2 and MRP3 protein could be an effective factor in judging the malignant degree in esophageal carcinoma.3. Experssion of MRP2 and MRP3 show obvious correlation in primary esophageal squamous cell carcinoma. It suggests that the cooperative expression of them has the same modulatory mechanism and plays a cooperation role in multidrug resistance.