Proliferative activity, p53 expression and apoptosis in pituitary adenomas: relationship to tumor behaviour

Abstract

Introduction: Pituitary adenomas are known to considerably vary from the stand point of their intrinsec aggressiveness that might imply a different therapeutical approach. The aim was to estimate the relationship between proliferative activity (Ki67), p53 expression, apoptosis and pituitary tumor behaviour. Materials and methods: Immunohistochemical analysis of Ki67 and p53 expression were performed in 50 paraffin-embedded pituitary adenomas: 28 functioning; 22 non-functioning; 34 invasive adenomas. Apoptotic index (AI) was determined in 24 adenomas by the in situ end-labeling technique (TUNEL). Results: Ki67 expression in total adenomas was 3,68% (significantly higher in functioning comparatively with non-functioning pituitary adenomas –4.45±0.5% versus 2.62±0.47%). We noticed a positive correlation between the proliferative activity and the tumoral invasiveness (Ki67 labeling index 4.82±0.4% in invasive and 1.25±0.3% in non-invasive adenoma). p53 nuclear positivity was identified in 50% of the invasive adenomas and only 5% in non-invasive adenomas, with a positive correlation between p53 and proliferative activity (Ki67: 5.58±0.4 in p53 positive versus 2.60±0.47% in p53 negative tumors). Apoptosis was found in 60% of tumors, higher in some of the invasive ones, with a positive correlation between the proliferation rates and apoptotic indices (AI: 4.54±1.22 in total versus 5.42±1.46 in invasive pituitary adenomas). Also, some differences were recorded in functioning and non-functioning adenomas (AI: 5.14±1.62 versus 3.70±1.92). Conclusions: The data suggest that the assessment of proliferation, p53 expression and apoptosis might be used to evaluate tumor behaviour and susceptibility of adenomas to therapy.