Molecular characterization of muscle-invasive urothelial bladder carcinoma.

Abstract

The molecular profile of muscle-invasive bladder tumors has prompted their classification into molecular subtypes, which exhibit different associations with treatment response and patient survival. To characterize muscle-invasive urothelial carcinoma of the bladder into molecular subtypes by immunohistochemical study. A panel of immunohistochemical markers composed of 5 antibodies was used: CK 5/6, GATA 3, p53, Cerb2/neu, EGFR. Cases were classified into luminal (CK5/6 positive and GATA3 negative) or basal (CK5/6 negative and GATA3 positive) subtype; the p53, Cerb2/neu and EGFR subtype of the cases was assigned according to the immunostaining pattern. Of the 14 patients evaluated, 79% (11) had luminal subtype tumors and 21% (3) basal subtype tumors, 58% conventional subtype urothelial carcinoma, positive expression (3+) of Cerb2/neu in 21%, positive EGFR in 50%, 57% with mutated p53. Regarding the luminal tumors, 14% were glandular histological subtype, 18% Cerb2/neu positive, 45% EGFR positive and 55% p53 mutated; in contrast, basal tumors showed clear cell subtype in 66.66% of cases, 33% Cerb2/neu positive, 67% EGFR positive and 67% p53 mutated. Molecular classification using immunohistochemical markers is feasible and useful, allowing for a better selection of patients who are candidates for neoadjuvant chemotherapy, considering the higher response rates in basal-like tumors. Luminal and basal-like tumors present positive expression of Cerb-2-neu (HER2/NEU) and EGFR; these markers are useful for directing therapeutics in future research.