Poor Prognosis and a Distinctive Genetic Profile Define Muscle- Invasive Transitional Cell Carcinoma of the Bladder with Single-File Infiltration Pattern
<p>Background: Histologic patterns have been demonstrated prognostically useful in transitional cell carcinomas (TCC) of the bladder, especially for the distinction between superficial and invasive neoplasms. No information is available on the prognostic significance and genetic profile of invasive patterns in muscle-invasive TCC.<br>Methods: Seventy-twomuscle-invasiveTCC of the bladder were histologically evaluated regarding a pondered histologic grade (low vs. high), and MIB-1 index. The infiltrationpattern was assessed in the deep compartment and classified according to the predominant pattern as ‘solid’ (macronodules or diffuse infiltration effacing the muscle fibers) or ‘single-file’ (S-F = single-cell tumor infiltration dissecting the muscle and inducing a dense stromal reaction). DNA was extracted from at least 2 samples per tumor and used to analyze the microsatellite pattern of TP53, RB1, WT1, and NF1 by PCR - denaturing gradient gel electrophoresis. The data were statistically evaluated by ANOVA and Fisher’s exact test.<br>Results: Solid TCC revealed significantly higher MIB- 1 index than SF infiltrating TCC, tended to show higher proportion of low-grade TCC, and longer survival.<br>The genetic profile demonstrated significant differences only for RB1 -and NF1 abnormalities (present in solid TCC), and more genetic alterations in solid TCC.<br>Conclusions: Solid infiltration in muscle-invasive TCC correlates with higher proliferation, higher incidence of RB1 and NF1 abnormalities,and longer survival.</p