Abstract: Objective: To investigate th application value of cyclooxygenase(COX-2),vascular endothelial growth factor (VEGF),and p16 gene and expression in endometrial cancinoma and endometrial polyp for differential diagnosis. Methods: A total of 240 patients with endometrial lesions were selected,including 30 cases of endometrial cancer diagnosed by histopathology as the malignant group and 210 cases of endometrial polyps as the benign group.The expression of COX-2,VEGF,and p16 genes and the diagnostic efficacy of the combination of the three genes were compared between the two groups.The relationship between the expression of COX-2,VEGF,and p16 genes and the clinical pathological characteristics of endometrial cancer,as well as the correlation between the expression of COX-2,VEGF,and p16 genes,were analyzed. Results: The positive rates of COX-2 and VEGF gene expression in the malignant group were higher than those in the benign group (P<0.01),while the positive rate of p16 gene expression was lower than that in the benign group (P<0.01).The combination of COX-2,VEGF,and p16 gene expression identified 32 cases of malignant endometrial lesions and 208 cases of benign endometrial lesions.The sensitivity and negative predictive value of the combination of COX-2,VEGF,and p16 gene expression for the differential diagnosis of benign endometrial cancer were higher than those of p16 gene expression alone (P<0.01),and the specificity,positive predictive value,and accuracy were higher than those of COX-2,VEGF,and p16 gene expression alone (P<0.01).The expression of COX-2 gene in endometrial cancer patients was positively correlated with histological grade,myometrial invasion,and lymph node metastasis (P<0.05 to P<0.01).The expression of VEGF gene in endometrial cancer patients was positively correlated with FIGO stage,histological grade,myometrial invasion,and lymph node metastasis (P<0.05).The expression of p16 gene in endometrial cancer patients was negatively correlated with histological grade and myometrial invasion (P<0.05).The expression of COX-2 and VEGF genes was negatively correlated with the expression of p16 gene in endometrial cancer patients (P<0.01),and the expression of COX-2 and VEGF genes was positively correlated (P<0.01). Conclusions: Patients with endometrial cancer have higher positive expression of COX-2 and VEGF,and lower expression of p16 gene.The combination of the three genes has high diagnostic efficacy for distinguishing benign from malignant endometrial lesions.