Expressions Of LRP And MRP Gene In Esophageal Carcinoma And Its Correlation With Pathological Characteristics

Esophageal carcinoma is a kind of common malignant carcinoma in our country, especially in Henan province. Chemotherapy is the basic therapy for esophageal carcinoma patients who have had operation or who have not had the surgical opportunity to do operation, but resistance of cancer cells to the anti-cancer drugs is the main factor that reduces the efficiency of the chemotherapy, and the most cases that caused the defeat of chemotherapy to esophageal carcinoma is multidrug resistance(MDR).Lung resistance protein (LRP) is a molecular newly found in recent years associated with multidrug resistance. LRP is a non-p-glycoprotein. As the major vault protein in human, it may mediate multidrug resistance by regulation the nuclecytoplastic and vesicular transport of drugs.LRP expression has been found in several malignant blood diseases such as acute leukemia, multiple myeloma and other tumors such as ovarian carcinoma, malignant melanoma and so on. positive LRP expression in some malignant diseases appears to poor prognosis. We have not ever found thereports about the LRP expression in esophageal carcinoma.Multidrug resistance-associated protein(MRP) is another protein associated with cancer drug resistance. It was found that many normal tissues and tumor cells may express MRP, for example, it is high expression in CLL. MRP may also regulate vesicular transport of drugs besides of drug efflux pump, which is similar to LRP function. There are few reports about MRP in esophageal carcinoma.The aim of this syudy is to determine their expression and clinical significance of LRP and MRP and their relation in esophageal carcinoma. By the methods of RT-PCR and immunohistochemistry, the expressions of LRP gene and MRP gene were detected in esophageal carcinoma tissuea and corresponding normal tissues. It was observed that expressions of LRP and MRP(mRNA and protein) correlated with pathological characteristics. The correlation between LRP and MRP in the carcinogenesis and development of esophageal carcinoma(EC) could be further discussed. In addition, the paper studied the funtion of LRP and MRP and the correlation of them both in multidrug resistance and development of esophageal carcinoma.Materials and methods:1.The expressions of LRP and MRP protein were detected in 81 cases of surgically resected esophageal squamous carcinoma specimens and 78 cases of corresponding normal tissues by the method fo immunohistochemistry.2.The expressions of LRP and MRP mRNA were observed in 32 cases of surgically resected esophageal squamous carcinoma specimens and 32 cases of corresponding normal tissues by the method of RT-PCR3. Statistical analysis:All the data were analyced by SPSS 11.0 statistical package, including t test, Chi-square and Fisher exact test. The accepted level of significance was a =0.05.All p-values presented are two-sides.Results:1.The expressions of LRP protein were higher significantly in carcinomatissues than those in normal tissues(/M). 02). It was not found that LRP protein expressions were correlated with carcinoma differentiation, the depth of invasion and lymph node metastasis(P>0. 05).2. The expressions of LRP mRNA were higher significantly in carcinoma tissues than those in normal tissues (P=0. 03). It wan not observed that LRP mRNA expressions were correlated to carcinoma differentiation, the depth of invasion and lymph node metastasis(P>0. 05).3.There was not a significant correlation between expressions of LRP protein and LRP mRNA (P>0.05).4. The expressions of MRP protein were higher significantly in carcinoma tissues than those in normal tissues(/M). 012). The expressions of MRP in deeper invasing group and group with lymph node metastasis were significantly higher than those in superficial invasing group and group without lymph node metastasis(fKO. 05).It was not observed that MRP protein expressions were related to carcinoma differentiation(P>0. 05).5. The expressions of MRP mRNA showed no difference between esophageal normal tissues and carcinoma tissues (P>0. 05). It was not found that MRP mRNA expressions were related to carcinoma differentiation, the depth of invasion and lymph node metastasis(P>0. 05).6.There was no significantly correlation between expressions of MRP protein and MRP mRNA(P>0. 05).7. There is a significant correlation between expressions of LRP protein and MRP protein in carcinoma tissues with higher differentiation(/M). 027). It was not found that the significant correlation between LRP and MRP protein was related to invasion depth and lymph node metastasis (P>0. 05).Conclusion:l.The expressions of LRP and MRP are higher in carcinoma tissues than those in normal tissues.lt is indicated that the higher expression of LRPand MRP is related to the primary multidrug resistance in esophageal squamous cell carcinoma. LRP may involve in esophagus carcinogenesis.2. The high expression of LRP may involve in esophagus carcinogenesis.Expressions of LRP(mRNA and protein) are not related to carcinoma differentiation, the depth of invasion and lymph node metastasis, It is indicated that LRP is independent of morphlogic prognostic indexes without correlation between their expressions and pathological characteristics.3. It is indicated that the overexpression of MRP protein may involve in esophagus carcinogenesis, progression and the formation of metastasis. MRP protein could be an effective factor in judging the malignant degree in esophageal carcinoma.4. The overexpressions of MRP protein and LRP protein in carcinoma tissues are not approved in the mRNA level. It is suggested that it may resulted from the up-regulation in translational level or the increased protein stability.5.There is no significant correlation in pathological characteristics between LRP protein and MRP protein. It could be indicated that they do not play a cooperative role in esophagus carcinogenesis and progression.