The clinicopathological features and importance of p53, Rb, and mdm2 expression in phaeochromocytomas and paragangliomas

Abstract

Aims: Phaeochromocytomas and paragangliomas are uncommon. The aims of this study were to analyse the characteristics and the possible roles of p53, Rb, and mdm2 alterations in these tumours.

Methods: The clinicopathological features of 65 patients (31 men, 34 women) with phaeochromocytomas or paragangliomas were analysed. The tumours were studied for the expression of p53, Rb, and mdm2 by immunohistochemical methods.

Results: Thirty nine of the patients had phaeochromocytomas and 26 had paragangliomas. Bilateral tumours were noted in eight of the patients and malignant tumours were seen in 13. Paragangliomas were often small, non-functional, and presented incidentally, whereas phaeochromocytomas were usually large, functional, and symptomatic. p53 overexpression, loss of Rb expression, and mdm2 overexpression were seen in four, 43, and 37 of the patients, respectively. Three of the four patients with p53 overexpression had bilateral tumours. Loss of Rb expression was often found in phaeochromocytomas, whereas mdm2 overexpression was more frequently seen in paragangliomas. The 10 year survival rate of patients with malignant tumours was 45%. Two patients died of tumour metastases more than 10 years after resection of the primary tumours.

Conclusions: Phaeochromocytomas and paragangliomas had distinctive clinical features and genetic alterations. The prognosis of patients with these tumours was related to the malignant potential. p53 overexpression, more common in bilateral phaeochromocytomas and paragangliomas, could be a marker for this tumour subgroup.

Figure 1 Overall survival curves of patients with phaeochromocytomas/paragangliomas. (A) Benign versus malignant tumours, p = 0.0001; (B) p53 overexpression (positive versus negative), p = 0.04; (C) Rb expression (positive versus negative), p = 0.80; mdm2 overexpression (positive versus negative), p = 0.26.