Apoptosis in thyroid neoplasms: relationship with p53 and bcl-2 expression

Cell gain and loss occurs concurrently in tumours. Apoptosis may play a major role in determining the growth and aggressiveness of the tumours. The aim of this study was to investigate whether apoptosis is related to the degree of differentiation and expression of mutated p53 and bcl-2 in thyroid neoplasms.

Fifty-three thyroid tumours of various histological types and 10 multinodular goitres were investigated semiquantitatively for the presence of apoptosis using a DNA end ligase method. Simultaneously, quantitative immunostaining was performed for bcl-2 and p53, two known regulators of apoptosis. No apoptosis was detected in normal thyroid tissues, multinodular goitres and in four follicular adenomas, all of which were positive for bcl-2. On the other hand, two anaplastic and one insular carcinomas showed marked increase in apoptosis along with intense p53 positivity and bcl-2 negativity. The majority of the follicular carcinomas showed results similar to that of follicular adenomas. No apoptosis was detected in 41% of papillary carcinomas, the majority of these being p53 negative and bcl-2 positive. Forty-four per cent of the papillary carcinomas demonstrated low apoptosis rate, with variable bcl-2 positivity and mostly negative for p53. Fifteen per cent of papillary carcinomas showed a high apoptosis rate. They were p53 negative and mostly negative for bcl-2. The differences of staining in various tumours with respect to p53, bcl-2 and apoptosis were statistically significant. Correlation analysis demonstrated a significant relationship between apoptosis and bcl-2 expression in thyroid tumours (P < 0.001), whereas no relationship was seen with p53.

These data suggest that bcl-2 expression in thyroid neoplasms is related to apoptosis, p53 expression is associated with high grade thyroid tumours, but may not be important in the apoptotic pathways in all thyroid tumours.