The value of Ki-67 antigen expression in tissue microarray method in prediction prognosis of patients with endometrioid endometrial cancer

Abstract

Objectives: To assess the prognostic significance of Ki-67 expression in the tissue microarray method (TMA) for disease free survival (DFS) and overall survival (OS) in endometrioid endometrial cancer (EEC). Material and methods: The study examined 159 consecutive patients aged 37-86 (62.82±9.95) with EEC stages I-III according to FIGO, treated surgically at the Pirogow Memorial Hospital of Lodz between 2000 and 2007. Afterwards they were subsequently treated and examined at the Regional Cancer Center, Copernicus Memorial Hospital of Lodz. Tissue cores 2 mm in size, in duplicate, were taken from the formalin-fixed and paraffin-embedded tissue donor blocks from surgery, and constructed into the TMA recipient blocks. Using TMA method, the relationship between Ki-67 expression, DFS and OS was examined. DFS was defined as a period from primary surgery until relapse. OS was defined as a period from primary surgery until the end of the follow-up (60 months) or until the death of the patient. The study was approved by the Ethics Committee of the Medical University of Lodz (RNN/82/11/KE; KE/1673/12). Results: The follow-up time varied between 3 - 60 months (51.42±15.87). In 31 patients (19.50%) the relapse of was diagnosed 1–59 months (24.97±16.08) after commencement of the treatment. During follow-up 32 patients (20.12%) died. DFS and OS were 80.50% and 79.88%, respectively. The lack of Ki-67 expression was found in 37 cases (23.27%) while in 122 patients (76.73%) the expression was present (p<0.001). The expression of Ki-67 in 1-10%, 11-20% and >20% was present in 76 cases, 26 cases and 20 cases, respectively. Positive correlation between the expression of Ki-67 and staging was present (r=0.353; p<0.001). In EEC patients with no relapse diagnosed during follow-up the expression of Ki-67 was present in 7.63±7.57% of EEC cells, when compared to 23.06±22.93% in EEC patients in relapsed disease (p<0.001). The relationship between increased Ki-67 expression and increased grading was not statistically significant (r=0.149; p=0.061). The expression of Ki-67 did not depend on patient age (r=0.040; p=0.617). In univariate analysis negative correlation was found between the expression of Ki-67 and DFS (p<0.001) and OS (p=0.01). In multivariate analysis worse DFS was related to higher staging of EEC (p<0.001) and increased expression of Ki-67 (p<0.001). Worse OS was related to higher staging in multivariate analysis (p<0.001). Ki-67 expression was not related to OS in multivariate analysis. Age of patients and grading of the EEC were not related to DFS and OS. Conclusions: The expression of the Ki-67 can significantly affect therapeutic decisions in selected EEC patients. The high Ki-67 expression in EEC patients is related to increased risk of relapse. The TMA technique is a good method for the assessment of the Ki-67 in studies conducted in EEC patients and makes it easier to carry out immunohistochemistry in large populations of patients.