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 renal pelvis and ureter, including dysplastic lesions, were studied for p53 and bcl-2 protein expression by immunohistochemistry. Twenty-one patients were also studied for p53 gene mutations by direct sequencing and for bcl-2 gene rearrangement by Southern blot analysis. Overexpressed p53 protein was detected in 26 cases (27.7 per cent). bcl-2 immunostaining was observed in 21 tumours (22.3 per cent), including four cases with labelling for p53. Furthermore, the dysplastic lesions surrounding 19 p53-positive tumours also stained for p53. bcl-2 expression was also detected frequently in dysplastic lesions adjacent to 14 bcl-2-positive TCCs. Positive reactions of dysplastic lesions were also found adjacent to 37 bcl-2-negative tumours. p53 point mutation was detected in 6 of 21 cases. Five of the six cases were positive for p53 protein. blc-2 positivity was detected in 3 of 21 tumours, without bcl-2 gene rearrangements in the major breakpoint region. Overexpressed p53 protein was frequently detected in both high-grade (P < 0.05) and invasive tumours (P < 0.05). In three cases of p53-positive non-papillary invasive tumours, bcl-2 was found in non-invasive portions, but was not present in invasive areas. These findings suggest that overexpression (mutation) of p53 and/or bcl-2 protein may be early events in tumourigenesis and that p53 alterations in particular are essential for the maintenance of a malignant phenotype in tumour development.
Furihata
M
M
Department of Pathology II, Kochi Medical School, Nankoku, Japan.
Sonobe
H
H
Ohtsuki
Y
Y
Yamashita
M
M
Morioka
M
M
Yamamoto
A
A
Terao
N
N
Kuwahara
M
M
Fujisaki
N
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015139:Blotting, Southern; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000378:metabolism; D005260:Female; D016158:Genes, p53; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014516:Ureteral Neoplasms / Q000235:genetics / Q000378:metabolism*
D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53