Prognostic value of microsatellite instability (MSI) and PTEN expression in women with endometrial cancer: results from studies of the NCIC Clinical Trials Group (NCIC CTG)

Abstract

Aim: The impact of PTEN status and microsatellite instability (MSI) on the prognosis of women with endometrial cancer is controversial. The aim of this study was to investigate MSI and PTEN expression in two patient populations using data from NCIC CTG studies.

Methods: Archival paraffin embedded tumour from women with endometrial cancer enrolled in NCIC CTG studies: EN5 (stage I/II) and IND 126, 148 and 160 (advanced/recurrent disease) were examined for MSI using BAT25/26 and for PTEN expression using immunohistochemistry. PTEN and MSI status were correlated with clinicopathologic variables and survival using data from NCIC CTG trial databases.

Results: PTEN and MSI results were available from 128 and 163 patients, respectively. MSI+ tumours were more common in women enrolled in EN5 compared to the IND studies (p=0.01). PTEN negative tumours were associated with improved survival in both univariate (hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.32-0.94; p=0.03) and multivariate (adjusted HR 0.54, 95% CI 0.30-0.96; p=0.03) analyses in women enrolled in IND studies. Microsatellite stable tumours were associated with an improved prognosis in univariate (HR 0.18, 95% CI 0.06-0.51; p<0.0001) and multivariate (adjusted HR 0.16, 95% CI 0.05-0.5; p<0.0001) analyses in women enrolled in EN5. There was no significant correlation between MSI and PTEN status.

Conclusions: PTEN negative tumours in women with advanced disease are associated with improved survival. MSI+ tumours are more common in early stage disease and in this group of women are associated with a worse prognosis.