Frequent loss of 17p, but no p53mutations or protein overexpression in benign and malignant pheochromocytomas

Autor: Petri, Bart-Jeroen, Speel, Ernst-Jan M, Korpershoek, Esther, Claessen, Sandra M H, van Nederveen, Francien H, Giesen, Vivian, Dannenberg, Hilde, van der Harst, Erwin, Dinjens, Winand N M, de Krijger, Ronald R
Zdroj: Modern Pathology; April 2008, Vol. 21 Issue: 4 p407-413, 7p
Abstrakt: Genetic changes in the tumorigenesis of sporadic pheochromocytomas are poorly understood, and there are no good markers to discriminate benign from malignant pheochromocytomas. p53is a tumor suppressor gene and aberrations in this gene are frequently found in many tumor types. The role of p53in pheochromocytoma tumorigenesis is unclear, with some studies suggesting that p53mutations can be used to discriminate benign from malignant pheochromocytomas while other studies do not find such an association. Because most of these investigations were hampered by small series of tumors and the use of varying methods, we have performed a comprehensive analysis of p53aberrations in a large series of pheochromocytomas. Comparative genomic hybridization analysis of 31 benign and 20 malignant tumors showed loss of the p53locus at chromosome 17p13.1 in 2 3/51 (45%) cases, and most of these results were confirmed by fluorescence in situhybridization. Forty-three tumors, including the malignant tumors and the tumors with loss of the p53locus, were analyzed for p53mutations in exons 5–8, but none were found. Furthermore, p53 immunohistochemistry on 35 cases revealed strong nuclear p53 expression in only two pheochromocytoma metastases, all other tumors being negative. We conclude that, although there is frequent loss of the p53locus on 17p, the p53gene does not appear to play a major role in pheochromocytoma tumorigenesis.
Databáze: Supplemental Index