Microsatellite instability as predictor of survival in patients with invasive upper urinary tract transitional cell carcinoma.
Rouprêt M., Fromont G., Azzouzi AR., Catto JW., Vallancien G., Hamdy FC., Cussenot O.
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.