Recurrent astrocytic tumours--a study of p53 immunoreactivity and malignant progression

Recurrence and progression to higher grade lesions are characteristic of the clinical course of astrocytic tumours. Though p53 gene mutation is an important initiating event in astrocytic tumourigenesis, its role in malignant progression remains controversial. We have therefore analysed p53 protein expression in paired histological samples from 48 cases of astrocytic tumours and their recurrences--29 diffuse astrocytoma, 10 anaplastic astrocytoma and 14 glioblastoma multiforme (GBM). Malignant progression at recurrence was noted in 93% of diffuse and 64% of anaplastic astrocytomas. An association was observed of p53 protein immunopositivity and malignant progression at recurrence. Thus, 27 of 48 (56%) primary tumours were initially p53 positive, while in recurrent tumours associated with malignant progression this frequency increased to 71% (34/48 cases). This was because seven of the 13 cases (4/8 diffuse and 3/5 anaplastic astrocytoma) that were initially p53 negative acquired immunopositivity on malignant progression at recurrence. In contrast, none of the 19 tumours that recurred to the same grade showed any change of p53 status at recurrence. Furthermore recurrence was associated with increase in the percentage of p53 immunopositive cells (p53 labelling index), which was also higher in tumours with progression. This new acquisition of p53 immunopositivity on progression at recurrence has not been documented in earlier studies in English language literature, though increase in p53 LI has been documented. Thus, this study conclusively indicates the role of p53 in malignant progression of astrocytic tumours. Also, it suggests a potential role of p53 LI in predicting malignant progression at recurrence because the highest initial LI was noted in those tumours which progressed to GBM as compared with those which recurred to the same grade or progressed to anaplastic astrocytoma. No correlation could, however, be demonstrated between p53 immunoreactivity and interval to recurrence.