Clinical implications and prognostic value of single and combined biomarkers in endometrial carcinoma

Abstract

Background: Endometrial carcinoma is one of the most common gynecological cancers and the incidence has been increasing. This study was to identify the relationship of estrogen receptor (ER), progestrone receptor (PR), P53 protein, Ki-67 and phosphatase and tensin homolog deleted on chromosome ten (PTEN) with endometrial carcinoma, the assessment of these biomarkers and their association with clinicopathological parameters was performed.

Methods: A total of 198 cases of primary endometrial carcinoma were investigated for ER, PR, Ki-67, P53, and PTEN antigens by immunohistochemical methods. The association of these markers with age, menopause status, histological type, FIGO stage, grading, depth of invasion, lymph node involvement and serum tumor marker was examined.

Results: The percentages of Ki-67- and P53-negative endometrial tumors were significantly higher in ER-positive compared with ER-negative tumors (both P = 0.000). The same trend was evident with PR status. The percentage of PTEN-positive tumors was significantly higher in PR-positive compared with PR-negative tumors (P = 0.021), but was no difference in tumors with different ER status. There was no clear association between PTEN positivity and clinicopathological parameters except more relevance with endometrioid histotype (P = 0.013). There was a statistically significant difference in the distribution of the different combined biological factors examined in disease-free survival.

Conclusions: ER and PR status were significant predictors with staging, grading and recurrence. P53 and Ki-67 expression were inversely correlated with both ER and PR expression and have more aggressive clinicopathological features. PTEN expression was inversely correlated with PR expression but not with ER expression. The combined type of ER+PR+P53-PTEN+ was in the majority in endometrial cancer and seemed to be related to better clinical outcome. The combination of ER-PR-P53+PTEN- represented the worst disease-free survival and was strongly associated with poorest survival rate.