INVASION OF THE BLADDER BY TRANSITIONAL-CELL CARCINOMA - ITS RELATIONTO HISTOLOGIC GRADE AND EXPRESSION OF P53, MIB-1, C-ERB B-2, EPIDERMAL GROWTH-FACTOR RECEPTOR, AND BCL-2

BACKGROUND. Although pathologic level of invasion and histologic grade are helpful in predicting the clinical outcome of transitional cell c arcinoma of the bladder, they also create uncertainty. Immunohistochem ical staining for p53, MIB-1, epidermal growth factor receptor (EGFR), c-erb B-2, and bcl-2 have shown promise as prognostic factors when ev aluated singly, although multivariate analyses that include histologic grade and the interactive effects of these markers have not been stud ied extensively. The authors have initiated a prospective study to det ermine whether these markers add prognostic information to that provid ed by level of invasion and histologic grade. This initial report deta ils how these five markers relate to invasion of the bladder after con trolling for the effects of histologic grade. METHODS. The authors eva luated 229 transitional cell carcinomas in 229 patients using the Worl d Health Organization grading schema and immunohistochemical staining with antigen retrieval for p53, MIB-1, EGFR, c-erb B-2, and bcl-2, and they related these markers to invasion after controlling for grade wi th a multivariate logistic regression model. RESULTS. Although Grades 2 and 3 were the most important for predicting invasion, Grade 2 tumor s that stained for either MIB-1 or p53 indicated a significantly great er probability of invasion than suggested by grade alone. bcl-2 and p5 3 had an opposing and interactive effect: when p53 was absent, the pre sence of bcl-2 implied less probability of invasion; but when both bcl -2 and p53 were present, the protective effect of bcl-2 was no longer observed. Although neither EGFR nor c-erb B-2 were as important as the other three markers in determining the risk of invasion, Grade 3 tumo rs that stained for one, and especially both, of these markers were le ss likely to be invasive. CONCLUSIONS. These five markers sort into th ree interactive pairs: MIB-1 and p53, bcl-2 and p53, and EGFR and c-er b B-2. MIB-1 and p53 together imply a greater probability of invasion. bcl-2 appears to have a dual role, which depends on the presence of a ccumulated p53. Finally, EGFR and c-erb B-2 related closely to each ot her and in Grade 3 tumors imply a lesser probability of invasion. It i s likely that combinations of markers, or correlations between markers and grades, will yield prognostic information that is more powerful t han what histologic grade alone can provide. (C) 1998 American Cancer Society.