[903] Correlation of Selected Somatic Mutations and Pathologic Stage in High Grade Urothelial Carcinomas

O Lin, D Solit, H Al-Ahmadie, A Heguy, VE Reuter, NM Ishill, M Milowsky. Memorial Sloan-Kettering Cancer Center, New York, NY

Background: Urothelial carcinoma is a common malignancy with a variable biology and natural history. The majority of patients are initially diagnosed with superficial cancer, however, 20-40% of patients either present with more advanced disease or progress after therapy for early stage disease. Genetic mutations are frequent in urothelial carcinomas and maybe associated with clinical outcome. Prior studies have shown that the most common somatic mutations in urothelial carcinomas, independent of grade, are FGFR3, RB1, PIK3CA, CDKN2A and HRAS. This study analyzes the correlation of the most common somatic mutations in urothelial carcinoma with pathologic stage.
Design: Frozen material from 137 cystectomy specimens with superficial and invasive urothelial carcinomas were retrieved from our institution tumor bank for analysis. Only cases with matched pair of tumor and normal tissue were included in this study. DNA was extracted from these specimens and submitted to Sanger Sequencing for FGFR3, RB1, PIK3CA, CDKN2A and HRAS and BRAF. PCR reactions were carried out with 10 ng of whole genome amplified DNA. All putative mutations were confirmed by a second PCR and sequencing reaction, in parallel with amplification and sequencing of matched normal tissue DNA. All traces for mutation calls were manually reviewed. Statistical analysis is performed using Fisher's exact test.
Results: The correlation of somatic mutations in urothelial carcinomas and pathologic stage is listed below. Interestingly, four percent of those patients with invasive disease at diagnosis had an FGFR3 mutation, while 18% of those who presented with superficial disease had an FGFR3 mutation.

Correlation of somatic mutations with pathology stage
MutationStage 0-1 (n=25)Stage 2 (n=29)Stage 3 (n=74)Stage 4 (n=6)PValue
FGFR36 (24%)5 (17%)4 (5%)0 (0%)0.04
BRAF1 (4%)0 (0%)4 (5%)1 (17%)0.25
PIK3CA3 (12%)5 (17%)9 (12%)0 (0%)0.81
TP533 (12%)3 (10%)11 (15%)2 (33%)0.48
RB0 (0%)0 (0%)2 (3%)1 (17%)0.19
CDKN2A0 (0%)0 (0%)3 (4%)0 (0%)0.63
Path Stage (stage 0-1: Tis, Ta, T1)

Conclusions: FGFR3 mutation status appears to be associated with a lower pathologic stage in high grade urothelial carcinomas. The other somatic mutations show no significant correlation with pathology stage in the same cohort.
Category: Genitourinary (including renal tumors)

Wednesday, March 24, 2010 1:00 PM

Poster Session VI # 141, Wednesday Afternoon


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