| Object: To evaluate expressions of multidrug resistance gene (MDR1), multidrug resistance related protein (MRP) gene, Topoisomerase II a (Topo II a ), mutant p53 protein, Bcl-2 and P21rasin non-small cell lung cancer(NSCLC) of different histological types and different differentiated degrees, lymph node metastasis and TNM staging, and investigate the relationship involved in these characters. Try to elucidate the probable mechanism of intrinsic multidrug-resistance of NSCLC.Methods: NSCLC from 113 untreated cases stored in Department of Pathology, Zhongnan Hospital, Wuhan University between 1996 and 2000 were available for this study. Expressions of MDR1 and MRP gene mRNA in paraffin-embedded cancer tissues were determined by in situ hybridization. And expressions of Topo II a , mutant p53 protein, Bcl-2 and P21ras were detected by S-P immunohistochemical method.Results: (l)The positive expressions of MDR1 and MRP were observed in 58 (51.3%) cases and 91(80.5%) cases of non-small cell lung cancer respectively. The positive expression of MRP in squamous carcinoma was significantly lower than in other histological subtypes ( x2=13.733, P<0.01) , while such difference was not found in the expression of MDR1. Both of MDR1 and MRP had no relationships with cell differentiation, lymphatic metastasis and TNM staging. The positive co-expression of MDR1 and MRP (MDRl+/MRP+)was observed in 55 (48.8%) cases. In squamous carcinoma, the expression of MDR1+/MRP+ in middling differentiated was higher than in high and low differentiated, While the expression of MDR1+/MRP+ in high differentiated adenocarcinoma was the highest in different differentiated adenocarcinoma. And all of them had no statistic differences.(2) The positive percentage of Topo II was 60.2% (68/113) . The expression of Topo II a was significantly related with the histological types but not with differentiated degrees, lymph node metastasis and TNM staging. Topo II a in squamous carcinoma was expressed more highly than in other types of NSCLC (x2=6.598, P<0.05).(3) The positive percentages of mutant p53 protein, Bcl-2 and P21ras were 61.9% (70/113), 59.3% (67/113) and 70.8% (80/113) respectivly. The positive expression of Bcl-2 had a close relationship with the histological types ( x2=15.689, P<0.01) , especially the expression of Bcl-2 in squamous carcinoma was significant higher than in adenocarcinoma ( x2= 15.295, P<0.01) . All the three proteins had no observed relationship with cell differentiation, TNM staging and lymphatic metastasis. (3) There was a significant correlation between expressions of MDRl and MRP ( x2=15.535, P<0.01). The expression of P21ras had close relationships with MDR1( x2 =20.498 , P<0.01) and MRP (zx2=8.486, P=0.004). There was correlation between p53 and Bcl-2 ( x2=4.697, P<0.05).Conclusions: (l)The multridrug of NSCLC is determined by multiple factors and procedures, which include of MDRl, MRP, Topo II a , apoptosis-related gene, et al. (2)Both of MDRl and MRP play significant roles in intrinsic multidrug resistance of non-small cell lung cancer. And MRP gene would be more important than MDRl. The co-evaluate the expressions of MDRl and MRP may help to forecast the instrict multidrug condition of NSCLC better. (3)The reduced expression of Topo II a have relationship with the instrict multidrug of NSCLC. The expressions of MRP and Topo II a are two independent markers which are related with the chemotherapeutic sensitivity in squamous carcinoma. (4) P21ras, instead of P53 and Bcl-2, may be one of the agents that control the expressions of MDRl and MRP genes in multidrug resistance of NSCLC.
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