MLH1 and PMS2 Define Prognosis in Sporadic Urothelial Carcinoma of Renal Pelvis and Ureter.
Leire Andres, Laura Zaldumbide, Ayman Gaafar, Javier Gonzalez, Ana Garcia Tello, Javier C Angulo, Jose I Lopez. Hospital de Cruces, University of the Basque Country, Barakaldo, Spain; Hospital de Mendaro, Spain; Hospital de Getafe, Spain
Background: Most cases of hereditary non-polyposis colorectal cancer are associated to mismatch repair (MMR) gene mutations and microsatellite instability. Although a subset of urothelial carcinomas of the upper urinary tract has also been included in this syndrome, sporadic cases with this genetic anomaly also occur. Our aim is to evaluate the expression pattern of MMR gene products and their correlation with histological features and with prognosis in a retrospective series of urothelial carcinomas of renal pelvis and/or ureter homogeneously treated.
Design: Eighty sporadic urothelial carcinomas of the renal pelvis and/or ureter with long term follow-up were analysed for the protein expression of 4 MMR genes (hMLH1, hMSH2, hMSH6, and hPMS2). Classic histopathological parameters and angiogenesis (CD31) were re-evaluated and correlated with the immunohistochemical expression of these proteins (cut-off: <5% of stained nuclei).
Results: Males predominated in the series (66M/14F), with an average age of 67 years. Pure TCC histology was seen in 91.2% of the cases, with papillary phenotype in 85% and pushing border in the stromal invasion in 81.2%. Median follow-up was 37 months. MSH2 and MSH6 were expressed in 100% of the cases, MLH1 in 85%, and PMS2 in 72.5%. MLH1 and PMS2 expression was strongly associated (Cramer V, 0.60) and encompassed a shorter survival for both MLH1 (log-rank, p=0.0001) (Figure 1) and PMS2 (log rank, p=0.004) (Figure 2) MLH1 expression was associated to high tumour grade (p=0.009) and pT stage (p=0.05).
PMS2 was associated to infiltrative-type border of invasion in the stroma (p=0.008) and to increased neoangiogenesis (p=0.008).
Conclusions: The immunohistochemical expression of MLH1 and PMS2 may be considered as a new prognostic marker also in sporadic forms of upper urinary tract urothelial carcinoma.
Category: Genitourinary (including renal tumors)
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 120, Wednesday Morning