Microsatellite instability as predictor of survival in patients with invasive upper urinary tract transitional cell carcinoma.
OBJECTIVE
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.
Rouprêt
Morgan
M
Department of Urology, Tenon Hospital, AP-HP, Paris, France. mroupret@club-internet.fr
Fromont
Gaëlle
G
Azzouzi
Abdel-Rahmène
AR
Catto
Jim W
JW
Vallancien
Guy
G
Hamdy
Freddie C
FC
Cussenot
Olivier
O
D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D011379:Prognosis; D015996:Survival Rate; D014516:Ureteral Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality
C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein