| Objective:To investigate the expression levels of immunohistochemical markers Ki-67,P53,P16,WT-1,Pax-8 and their combinations in patients with epithelial ovarian cancer and their relationship with clinicopathological features and prognosis,and to evaluate the predictive value and efficacy of Ki-67,P53,P16,WT-1,Pax-8and their combinations for metastasis,drug resistance,recurrence and prognosis,so as to provide basis for prognosis judgment of patients with epithelial ovarian cancer.Method:x The clinicopathological data of 243 patients with epithelial ovarian cancer who were initially treated in Henan Provincial People’s Hospital from January 2018 to January 2021 and received comprehensive staged surgery or cytoreductive surgery for ovarian cancer were collected and followed up regularly after operation.According to the results of Ki-67,P53,P16,WT-1 and Pax-8 in the postoperative immunohistochemical report,SPSS26.0 was used to analyze the data,Chi-square test was used to analyze the relationship between immunohistochemical markers and clinical pathological characteristics of patients,Kaplan-Meier method was used to describe the survival curve,and Log-rank test was used to test the difference.Cox regression model was used for univariate and multivariate analysis,decision tree was used for classification,and receiver operating characteristic curve(ROC)and receiver operating characteristic curve area(AUC)values were used to compare the predictive efficacy of immunohistochemical markers and combinations on metastasis,drug resistance,recurrence and prognosis of epithelial ovarian cancer.The difference was statistically significant(P<0.05).Result:1.The relationship between immunohistochemical markers and clinicopathological features of epithelial ovarian cancer: The markers related to pathological types are Ki-67,P53,P16 and WT-1;The markers related to the degree of tissue differentiation are Ki-67,P53,P16 and WT-1.The markers related to FIGO staging are Ki-67,P53,P16,WT-1 and Pax-8.The marker associated with ascites is P53;The markers related to lymph node metastasis are Ki-67,P53,WT-1 and Pax-8.The markers related to distant metastasis are Ki-67,P16 and WT-1.The markers related to drug resistance are P53 and P16.2.The analysis of related factors of PFS showed: pathological type(P=0.006),degree of tissue differentiation(P=0.018),FIGO stage(P=0.000),ascites(P=0.024),lymph node metastasis(P=0.000)and distant metastasis(P=0.000)are related to PFS,The difference is statistically significant;FIGO stage(P=0.021),Ki67(P=0.009)and P53(P=0.015)are independent risk factors for PFS in patients with epithelial ovarian cancer.3.The analysis of related factors of OS showed:the degree of tissue differentiation(P=0.012),FIGO staging(P=0.000),ascites(P=0.025),lymph node metastasis(P=0.015),distant metastasis(P=0.000)and Ki67(P=0.001)are related to OS,The difference is statistically significant;FIGO stage(P=0.041),distant metastasis(P=0.036)and P53(P=0.022)are independent risk factors for OS in patients with epithelial ovarian cancer.4.Combination analysis of immunohistochemical markers: The effective combination for predicting distant metastasis is Ki67(+)/P16(+)/WT-1(+),and the distant metastasis rate of patients with epithelial ovarian cancer who express this combination is 23.0%,which is significantly higher than that of patients who do not express this combination(1.7%),and the difference is statistically significant(P< 0.001);The effective combination of Ki67(+)/ P53(+)is used to predict recurrence,and the PFS of patients with epithelial ovarian cancer expressing this combination is significantly lower than that of patients without this combination,with statistical significance(P< 0.001).5.Analysis of the predictive efficacy of immunohistochemical markers and combinations for the prognosis of epithelial ovarian cancer: the AUC value of Ki67(+)/P16(+)/WT-1(+)combination was 0.739,which was higher than that of a single immunohistochemical marker,among which the AUC value of P16 was the highest(0.637)and that of WT-1 was the lowest(0.604);the AUC value of Ki67(+)/P53(+)combination was 0.778,which was higher than that of a single immunohistochemical marker,among which the AUC value of P53 was the highest(0.731)and that of WT-1 was the lowest(0.522).Conclusions:1.Ki-67,P53,P16,WT-1 and Pax-8 are related to the clinicopathological features of epithelial ovarian cancer,which can preliminarily reflect the progress and malignant degree of epithelial ovarian cancer.2.P53 and P16 are related to drug resistance of epithelial ovarian cancer,which can reflect patients’ response to chemotherapy to some extent,and hopefully become biomarkers for predicting drug resistance of epithelial ovarian cancer.3.Patients with positive expression of Ki-67,P16 and WT-1 are more likely to have distant metastasis,while patients with positive expression of Ki-67 and P53 have shorter PFS and are more likely to relapse.4.Ki67 and P53 are independent risk factors for PFS in epithelial ovarian cancer.P53 is an independent risk factor for epithelial ovarian cancer OS.5.Ki67(+)/P16(+)/WT-1(+)combination is superior to a single immunohistochemical marker in predicting distant metastasis of epithelial ovarian cancer,and can be used as a candidate marker combination for predicting distant metastasis of epithelial ovarian cancer;the combination of Ki67(+)/P53(+)is superior to a single immunohistochemical marker in predicting the recurrence of epithelial ovarian cancer,and patients who express this combination are more prone to recurrence,which should be highly concerned in clinic. |
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