DETECTION OF P53 AND BCL-2 PROTEIN IN CARCINOMA OF THE RENAL PELVIS AND URETER INCLUDING DYSPLASIA

Ninety-four patients with transitional cell carcinoma (TCC) of the ren al pelvis and meter, including dysplastic lesions, were studied for p5 3 and bcl-2 protein expression by immunohistochemistry. Twenty-one pat ients were also studied for p53 gene mutations by direct sequencing an d for bcl-2 gene rearrangement by Southern blot analysis. Overexpresse d p53 protein was detected in 26 cases (27.7 per cent). bcl-2 immunost aining was observed in 21 tumours (22.3 per cent), including four case s with labelling for p53. Furthermore, the dysplastic lesions surround ing 19 p53-positive tumours also stained for p53. bcl-2 expression was also detected frequently in dysplastic lesions adjacent to 14 bcl-2-p ositive TCCs. Positive reactions of dysplastic lesions were also found adjacent to 37 bcl-2-negative tumours. p53 point mutation was detecte d in 6 of 21 cases. Five of the six cases were positive for p53 protei n. bcl-2 positivity was detected in 3 of 21 tumours, without bcl-2 gen e rearrangements in the major breakpoint region. Overexpressed p53 pro tein was frequently detected in both high-grade (P<0.05) and invasive tumours (P<0.05). In three cases of p53-positive non-papillary invasiv e tumours, bcl-2 was found in non-invasive portions, but was not prese nt in invasive areas. These findings suggest that overexpression (muta tion) of p53 and/or bcl-2 protein may be early events in tumourigenesi s and that p53 alterations in particular are essential for the mainten ance of a malignant phenotype in tumour development.