Research On The Expressions And Clinical Significance Of P-GP,MRP1,LRP And GST-π In Yolk SAC Tumor

Objective:Malignant germ cell tumors occur in childhood at a rate of 2 to 3 cases per million children, and Yolk sac tumor accounts for the most(62.7%) of malignant germ cell tumors. Before the introduction of effective combination chemotherapy, the prognosis for patients with yolk sac tumor was worse, which 3-year survival rate was 13%. And after the combination chemotherapy had been executed in clinic, the 5-year survival rate of patients with yolk sac tumor in stage Ⅰwas 68.1%. However, the prognosis of patients in stagesⅡto Ⅳ was still worse. The multidrug resistance (MDR) of tumor cells caused the usual dose chemotherapy failed, and the tumor cells could not be killed effectively. Finally, relapse of the tumor happened. So it is very important to improve the effect of combination chemotherapy. Research on the mechanisms of the MDR of yolk sac tumor will be beneficial for choosing the protocol of combination chemotherapy and predicting the effects of therapy, and be value to improve the curative effects of patients with yolk sac tumor in stagesⅡto Ⅳ.Methods: The expressions of P-gp,MRP1,LRP and GST-π were detected by immunohistochemistry staining in 37 cases of yolk sac tumor.Results: (1)In all cases, positive and strong positive expressions of the different MDR-related proteins were: 36(97.3％)and 28(75.7％)(P-gp), 25(67.6％)and 11(29.7％)(MRP1), 36(97.3％)and 21(56.8％)(LRP), 34(91.9％)and 26(70.3％)(GST-π). (2)In 37 cases, there are 13 patients in stage Ⅰand 24 patients in stages ⅡtoⅣ. Strong positive expressions of the different MDR-related proteins in cases of stage Ⅰand cases of stages ⅡtoⅣ were: 10(76％)and 18(75％) (P-gp); 3(23％),8(33％) (MRP1); 6(46％),15(63％) (LRP); 8(62％),18(75％)(GST-π). (3)The strong positive expressions of the four MDR-related proteins had nothing to do with the locus of yolk sac tumor. (4)The loose reticulate structure could be detected in all cases, and the strong positive expression rates of P-gp, MRP1, LRP and GST-π in it were 67%, 48%, 57% and 38% respectively( P＜0.05). Schiller-Duvall body was detected in 30 cases, and the strong positive expression rates of P-gp, MRP1, LRP and GST-π in it were 53%, 20%, 33% and 50% respectively( P＜0.05). Adenoidal structure was detected in 26 cases, and the strong positive expression rates of P-gp, MRP1, LRP and GST-π in it were 77%, 31%, 73% and 77% respectively(P＜0.05). Polyvesicular structure was detected in 16 cases, and the strong positive expression rates of P-gp, MRP1, LRP and GST-π in it were 56%, 31%, 38% and 56% respectively(P＞0.05). Papillary structure was detected in 15 cases, and the strong positive expression rates of P-gp, MRP1, LRP and GST-π in it were 33%, 27%, 20% and 33% respectively( P＞0.05). Cell rich Papilliferous structure was detected in 19 cases, and the strong positive expression rates of P-gp, MRP1, LRP and GST-π in it were 47%, 5%, 16% and 21% respectively( P＜0.05). (5)In cases with both Schiller-Duvall body and adenoidal structure, positive and strong positive expressions of alpha-fetoprotein were 5(33%) and 15(80%) ( P＜0.01 ).Conclusions: (1) The yolk sac tumor has the intrinsic drug resistance, caused by many drug resistance genes through different mechanisms. The over expressions of P-gp and GST-π in tissues were the main mechanisms for multidrug resistance of yolk sac tumor, and the expressions of MRP1 and LRP also took the synergistic actions. (2)There was no relationship between the expressions of 4 types of multidrug resistance genes in tissues and clinic staging of yolk sac tumor, which indicated the multidrug resistance of tumor might happen in different clinic staging. The aggressive level of the yolk sac tumor could be indicated by clinic staging, and the difference of MDR could be not. (3)The strong expressions of 4 multidrug resistance genes have nothing to do with the locus of the yolk sac tumor. (4) The formation of tissues in all cases were not same, and constituent ratio o...