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Altered expression of mdm-2 and its association with p53 protein status, tumor-cell-proliferation rate and prognosis in cervical neoplasia

Dellas, A. and Schultheiss, E. and Almendral, A. C. and Gudat, F. and Oberholzer, M. and Feichter, G. and Moch, H. and Torhorst, J.. (1997) Altered expression of mdm-2 and its association with p53 protein status, tumor-cell-proliferation rate and prognosis in cervical neoplasia. International journal of cancer, Vol. 74, H. 4. pp. 421-425.

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Official URL: http://edoc.unibas.ch/dok/A5249152

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Abstract

Recent results suggest that p53 inactivation is required for cervical-carcinoma development. The mdm-2 oncogene, which forms an auto-regulatory feedback loop with the normal p53 protein, has been found amplified in human carcinomas, thus abolishing the anti-proliferative function of p53. To investigate whether the mdm-2/p53 interaction plays a role in cervical neoplasms, we performed an immunohistochemical study in archival fixed, embedded specimens that included 178 pre-cancerous lesions (CIN) and invasive squamous-cell carcinomas of clinical stage IB. In addition to p53, we assessed the p53-associated protein, mdm-2, and the Ki-67 labelling index (LI). The presence of HPV was assessed by in situ DNA hybridization. Tumor expression of all nuclear proteins was scored as fraction of positive CIN or cancer nuclei. The analysis demonstrated a significant association of the Ki-67 LI with grade of atypia in cervical neoplasms. p53 accumulation and mdm-2 expression are higher in invasive carcinomas than in pre-cancerous lesions. No correlation was observed with HPV status. An inverse correlation was found between increased tumor-cell proliferation and mdm-2 expression in invasive carcinomas (p > 0.0001). mdm-2 expression was significantly associated with p53 accumulation (p > 0.02). However, the investigated nuclear proteins were not associated with overall survival in patients with invasive carcinomas. Cox stepwise-regression analysis revealed regional lymph node status and depth of invasion to be independent parameters.
Faculties and Departments:03 Faculty of Medicine > Bereich Spezialfächer (Klinik) > Gynäkologie und Geburtshilfe
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Spezialfächer (Klinik) > Gynäkologie und Geburtshilfe
03 Faculty of Medicine
UniBasel Contributors:Dellas, Athanassios
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Alan R. Liss
ISSN:0020-7136
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:23
Deposited On:22 Mar 2012 13:34

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