Introduction. Oncogene expression and cell proliferative activity are useful adjuncts in tumour pathology. Indeed, the immunohistochemical detection of p53, c-erbB-2, bcl-2 and c-myc proteins, as well as Ki67/MIB-1 antigen, and the analysis of the argyrophilic proteins associated with the nucleolar organiser regions (AgNORs) has provided a number of prognostic information in several human tumours. Ki67 antigen is expressed in the G1, S and G2 phases in cycling cells and indicates the tumour growth fraction. AgNOR quantity is inversely correlated to cell doubling time and may be regarded as a marker of the rapidity of tumour proliferation. To clarify the relationship between oncogene expression and the rapidity of tumour cell proliferation as well as growth fraction, we compared the expression of p53, c-erbB-2, bcl-2 and c-myc proteins to AgNOR quantity and MIB-1 antigen. Materials and Methods. Sections from 50 male breast carcinomas (MBC) and 62 non-invasive (pTa), low malignant potential or grade 1 papillary urothelial carcinomas were stained with the standardised AgNOR method and monoclonal antibodies MIB-1, DO7, CB11, bcl-2 124 and 9E11. Results. p53 immunoreactivity was associated with high AgNOR quantity both in MBC (p=0.009) and bladder carcinomas (p=0.04); it was also associated with high MIB-1 scores both in MBC (p<0.0001) and bladder tumours (p<0.0001). Association was found between c-erbB-2 expression and high AgNOR quantity in bladder tumours (p=0.03), but only a trend in MBC (p=0.1); no association was found between c-erbB-2 and MIB-1 scores in MBC and bladder neoplasm. bcl-2 expression was associated with low AgNOR quantity in MBC (p=0.04); it was not associated with MIB-1 scores in MBC and bladder tumours. c-myc immunopositivity was associated with high AgNOR quantity in MBC (p=0.006); a trend was detected for MIB 1 staining (p=0.1). By combining oncogene expression and proliferative activity, MBC patients with small AgNOR quantity, and negative p53, c-erbB-2 and c-myc immunostaining had the longest overall survival (100% at 10 year follow-up). Patients with bladder neoplasm showing small AgNOR quantity, negative p53 and positive c-erbB-2 immunostaining had the longest disease free survival time (80% at 79 months follow-up). Conclusions. Our results indicate that p53 overexpression is related both to the rapidity of cell proliferation, as assessed by AgNOR quantity, and tumour growth fraction, as assessed by MIB-1 scores, while c-erbB-2, c-myc and bcl-2 expressions are mainly related to the rapidity of cell proliferation. The combination of AgNOR quantity and oncogene expression may stratify patients with MBC or superficial bladder neoplasm into different risk groups.
Relationship between oncogene expression and cell proliferative activity in male breast and low grade urothelial carcinomas
PICH, Achille
2002-01-01
Abstract
Introduction. Oncogene expression and cell proliferative activity are useful adjuncts in tumour pathology. Indeed, the immunohistochemical detection of p53, c-erbB-2, bcl-2 and c-myc proteins, as well as Ki67/MIB-1 antigen, and the analysis of the argyrophilic proteins associated with the nucleolar organiser regions (AgNORs) has provided a number of prognostic information in several human tumours. Ki67 antigen is expressed in the G1, S and G2 phases in cycling cells and indicates the tumour growth fraction. AgNOR quantity is inversely correlated to cell doubling time and may be regarded as a marker of the rapidity of tumour proliferation. To clarify the relationship between oncogene expression and the rapidity of tumour cell proliferation as well as growth fraction, we compared the expression of p53, c-erbB-2, bcl-2 and c-myc proteins to AgNOR quantity and MIB-1 antigen. Materials and Methods. Sections from 50 male breast carcinomas (MBC) and 62 non-invasive (pTa), low malignant potential or grade 1 papillary urothelial carcinomas were stained with the standardised AgNOR method and monoclonal antibodies MIB-1, DO7, CB11, bcl-2 124 and 9E11. Results. p53 immunoreactivity was associated with high AgNOR quantity both in MBC (p=0.009) and bladder carcinomas (p=0.04); it was also associated with high MIB-1 scores both in MBC (p<0.0001) and bladder tumours (p<0.0001). Association was found between c-erbB-2 expression and high AgNOR quantity in bladder tumours (p=0.03), but only a trend in MBC (p=0.1); no association was found between c-erbB-2 and MIB-1 scores in MBC and bladder neoplasm. bcl-2 expression was associated with low AgNOR quantity in MBC (p=0.04); it was not associated with MIB-1 scores in MBC and bladder tumours. c-myc immunopositivity was associated with high AgNOR quantity in MBC (p=0.006); a trend was detected for MIB 1 staining (p=0.1). By combining oncogene expression and proliferative activity, MBC patients with small AgNOR quantity, and negative p53, c-erbB-2 and c-myc immunostaining had the longest overall survival (100% at 10 year follow-up). Patients with bladder neoplasm showing small AgNOR quantity, negative p53 and positive c-erbB-2 immunostaining had the longest disease free survival time (80% at 79 months follow-up). Conclusions. Our results indicate that p53 overexpression is related both to the rapidity of cell proliferation, as assessed by AgNOR quantity, and tumour growth fraction, as assessed by MIB-1 scores, while c-erbB-2, c-myc and bcl-2 expressions are mainly related to the rapidity of cell proliferation. The combination of AgNOR quantity and oncogene expression may stratify patients with MBC or superficial bladder neoplasm into different risk groups.
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