TP53 overexpression in recurrent endometrial carcinoma
Autor: | Patrick G. Groothuis, Manon van Engeland, Geeske C. Dam de Veen, Johanna M.A. Pijnenborg, Guido M.J.M. Roemen, Jan Willem Voncken, Leonie van de Broek, Jelte de Haan |
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Rok vydání: | 2006 |
Předmět: |
Nonsense mutation
Apoptosis medicine.disease_cause Exon Carcinoma Humans Medicine Missense mutation neoplasms Aged Aged 80 and over Mutation Paraffin Embedding business.industry Obstetrics and Gynecology Proto-Oncogene Proteins c-mdm2 Odds ratio Middle Aged medicine.disease Immunohistochemistry Endometrial Neoplasms Oncology Concomitant Cancer research Keratins Female Neoplasm Recurrence Local Tumor Suppressor Protein p53 business Carcinoma Endometrioid |
Zdroj: | Gynecologic Oncology. 100:397-404 |
ISSN: | 0090-8258 |
DOI: | 10.1016/j.ygyno.2005.09.056 |
Popis: | Objective. To study alterations within the p53 pathway in relation to the development of recurrent stage I endometrioid endometrial carcinoma. Methods. Paraffin-embedded tumor tissue of both primary and recurrent tumors from 44 patients with and 44 without recurrence was used for immunohistochemical analysis of TP53, hMdm2, P21 Waf1/Cip1 and M30. DNA was extracted, and mutation analysis of p53 (exon 5–8, 11) was performed by direct sequencing. Results. TP53 overexpression was significantly associated with recurrent disease: Odds Ratio 3.8 (95% CI: 1.5–9.8). Overexpression of TP53 was associated with lower staining indices (SI:0–9) of both hMdm2 and P21 in tumors of patients with recurrence, compared to controls: 2.0 ± 0.4 vs. 4.0 ± 0.8 and 1.9 ± 0.8 vs. 3.6 ± 0.8, respectively. Eight p53 missense mutations were identified in six patients with recurrence and two controls. One nonsense mutation was found in a patient with recurrence and one deletion in a control patient. Only a minority of TP53 overexpression cases could be explained by the presence of these p53 mutations. Conclusion. TP53 overexpression was significantly predictive for recurrent endometrial carcinoma, and mostly not correlated with p53 mutations. Concomitant low hMdm2 and P21 Waf1/Cip1 expression in tumors with overexpressed TP53 suggests a dysfunctional TP53-P21 Waf1/Cip1 pathway. |
Databáze: | OpenAIRE |
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