Expression of P53, MDM2 and Ki-67 antigens in soft tissue sarcomas.
The expression of P53 and MDM2 proteins was examined by immunohistochemistry in 115 soft-tissue sarcomas (STSs), including 32 malignant peripheral nerve sheath tumours, 27 liposarcomas, 18 leiomyosarcomas, 16 synovial sarcomas, 14 fibrosarcomas and 8 dermatofibrosarcomas, to investigate their possible association with clinicopathologic features and proliferative rate. Positivity for P53 and MDM2 was found in 9.7% and 28.1% tumours, respectively. The fraction of P53 and MDM2 positive tumours was the highest in leiomyosarcomas (16.7% and 17.2%, respectively) and the lowest in dermatofibrosarcomas (0% and 4.3%, respectively). Overall, P53(-)/MDM2(+) phenotype predominated (20.2%), while 7.9% of tumours were both P53 and MDM2 positive, and 1.8% of tumours were only P53 positive. P53 accumulation was associated with a high histological malignancy grade and a higher proliferative rate. MDM2 immunoreactivity was revealed in tumours of all malignancy grades and there was no association between MDM2 positivity and tumours proliferative activity. These results suggest that P53 overexpression underlays rather late events in the oncogenesis of STSs, which might be a determinant of their proliferative rate. In contrast, MDM2 deregulation seems to be an early rather than a late event in STSs, which may occur without involving stabilization and inactivation of P53 gene.
Department of Tumour Pathology, University Medical School, Lódź. jerszad@ck-sg.p.lodz.pl
A
A
Szadowska
B
B
Olborski
B
B
Harezga-Bal
M
M
Debiec-Rychter
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D051736:Proto-Oncogene Proteins c-mdm2; D012509:Sarcoma / Q000737:chemistry* / Q000276:immunology; D012983:Soft Tissue Neoplasms / Q000737:chemistry* / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2