Abstract
Amplification of the mdm-2 gene and overexpression of the mdm-2 protein might inactivate p53 function, and may have prognostic relevance. The present paper investigated the immunohistochemical overexpression of the mdm-2 and p53 proteins in 25 biopsy specimens of transitional cell bladder carcinomas (10 pT1 and 15 pT2 or higher stages). Five cases (20%) showed strong mdm-2 protein immunoreactivity in more than 5% of the tumor cells; 14 cases (56%) showed p53 immunoreactivity in more than 20% of the cells, and were considered as overexpressing p53 protein. Four of the five cases with strong mdm-2 immunoreactivity did not show p53 overexpression, and 13 of the 14 cases with p53 overexpression did not show mdm-2 immunoreactivity. Our data are consistent with the hypothesis that p53 overaccumulation (and hence possible p53 gene mutation) or mdm-2 overexpression (and hence possible mdm-2 gene amplification) may mirror two different and possibly complementary gene alterations, which might finally interfere with the control of cell proliferation and apoptosis. In this perspective, evaluation of the combined mdm-2/p53 protein phenotype in human bladder carcinomas could have prognostic relevance and give us better prognostic information than evaluation of the p53 protein alone.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Chilosi M, Doglioni C, Montagna L, Rigo A, Lestani M, Scarpa A, Menestrina F, Barbareschi M, Mariuzzi GM, Pizzolo G (1995) Abnormal expression of the p53-binding protein mdm2 in Hodgkin disease. Blood (in press)
Cordon-Cardo C, Latres E, Drobjak M, Oliva MR, Pollack D, Woodruff JM, Marechal V, Chen J, Levine AJ (1994) Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas. Cancer Res 54:794
Dei Toss AP, Doglioni C, Barbareschi M, Laurino L, Fletcher C (1993) p53 expression in soft tissue lesions. Histopathology 22:45
Finlay CA (1993) The mdm-2 oncogene can overcome wild-type p53 suppression of transformed cell growth. Mol Cell Biol 13:301
Kessis TD, Slebos RJ, Han SM, Keerti S, Bosch XF, Munoz N, Hedrick L, Cho KR (1993) p53 gene mutations and mdm2 amplification are uncommon in primary carcinomas of the uterine cervix. Am J Pathol 143:1398
Kovar H, Auinger A, Jug G, Aryee D, Zuobek A, Salzerkuntschik M, Gadner H (1993) Narrow spectrum and infrequent p53 mutations and absence of mdm2 amplification in Ewing tumours. Oncogene 8:2683
Ladanyi M, Cha C, Lewis R, Jhanwar SC, Huvos AG, Healey JH (1993) MDM2 gene amplification in metastatic osteosarcoma. Cancer Res 53:16
Leach FS, Tokino T, Meltzer P, Burrell M, Oliner JD, Smith S, Hill DE, Sidransky D, Kinzler KW, Vogelstein B (1993) p53 mutation and MDM2 amplification in soft tissue sarcomas. Cancer Res 53:2231
Marchetti A, Buttitta F, Girlando S, Dalla Palma P, Pellegrini S, Doglioni C, Bevilacqua G, Barbareschi M (in press) mdm2 gene alterations and mdm2 protein expression in breast carcinomas. J Pathol
Momand J, Zambetti GP, Olson DC, George D, Levine AJ (1992) The mdm2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69:1237
Mostofi FK, Sobin L, Torloni H (1973) International Histological Classification of Tumours, N: 10: Histological typing of urinary bladder tumours. World Health Organization, Geneva
Oliner JD, Kinzler KW, Meltzer PS, George D, Vogelstein B (1992) Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 358:80
Olson DC, Marechal V, Momad J, Chen J, Romocki C, Levine AJ (1993) Identification and characterization of multiple mdm-2 proteins and mdm-2-p53 protein complexes. Oncogene 8:2353
Preudhomme C, Quesnel B, Vachee A, Lepelley P, Collydhooghe M, Wattel E, Fenaux P (1993) Absence of amplification of mdm2 gene, a regulator of p53 function, in myelodysplastic syndromes. Leukemia 7:1291
Reifenberger G, Liu L, Ichimura K, Schmidt EE, Collins VP (1993) Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations. Cancer Res 53:2736
UICC (1987) TNM classification of malignant tumors. Springer, Berlin, Heidelberg New York
Zambetti GP, Levine AJ (1993) A comparison of the biological activities of wild-type and mutant p53. FASEB J 7:855
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Barbareschi, M., Girlando, S., Fellin, G. et al. Expression of mdm-2 and p53 protein in transitional cell carcinoma. Urol. Res. 22, 349–352 (1995). https://doi.org/10.1007/BF00296873
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00296873