Microsatellite instability as predictor of survival in patients with invasive upper urinary tract transitional cell carcinoma

Abstract

Objectives: To establish whether high microsatellite instability (MSI) (present in almost 20% of cases) and loss of MSH2 protein expression (sometimes used to predict MSI status) are prognostic factors of overall survival for patients with invasive upper urinary tract transitional cell carcinoma (UUT-TCC). UUT-TCC has a poor prognosis (overall survival less than 50% at 5 years).

Methods: The files of 80 patients who underwent nephroureterectomy for invasive UUT-TCC (Stage pT2 or worse) between 1990 and 2002 were reviewed. The following data were collated: age at diagnosis, prior history of cancer, tobacco consumption, tumor stage and grade, and disease progression. MSI was determined by polymerase chain reaction/fragment analysis and MSH2 protein expression by immunohistochemistry on retrieved tumor tissue.

Results: The median patient age was 71.5 years. The male/female ratio was 2.8. High MSI and loss of MSH2 expression were encountered in the tumors of 14 (17%) and 21 (26%) of the 80 patients, respectively. High MSI was significantly associated with patients with a better prognosis (Stage T2-T3N0M0; P = 0.02). The mean overall survival was 22.5 +/- 18 months (range 6 to 78). In univariate analyses, age, stage, tumor grade, high MSI, and loss of MSH2 expression were related to better overall survival (37 +/- 22 months, P = 0.003; 34 +/- 22 months, P = 0.02). Only stage, age, and high MSI were prognostic factors in a multivariate analysis (P < 0.05).

Conclusions: MSI and expression of MSH2 are useful prognostic factors in invasive UUT-TCC. However, other than age and stage, only MSI was an independent factor. High MSI indicates a better prognosis, especially in patients younger than 71 years with Stage T2-T3N0M0.