Ki-67 labelling index and invasiveness among anterior pituitary adenomas: analysis of 103 cases using the MIB-1 monoclonal antibody

Aims-To investigate the relation between proliferative activity of anterior pituitary adenomas, quantified by the Ki-67 labelling index, and their invasive behaviour. Methods-Expression of Ki-67 was evaluated in 103 anterior pituitary adenomas consecutively operated on in a 36 month period and correlated with surgical evidence of invasiveness. Results-Non-invasive (n = 65) and invasive (n = 38) adenomas were identified from surgically verified infiltration of sellar floor dura and bone. The wall of the cavernous sinus was infiltrated in 16 cases. Forty one adenomas were non-functioning and 62 functioning (24 prolactin, 21 growth hormone, 10 ACTH, seven mixed). The overall mean (SD) Ki-67 labelling index was 2.64 (3.69) per cent (median 1.5). The mean index was 3.08 (4.59) per cent in functioning and 1.97 (1.78) per cent in non-functioning tumours; 5.47 (9.52) per cent in ACTH adenomas and 2.33 (2.42) per cent in others (p = 0.01); 3.71 (5.17) per cent in invasive and 2.01 (2.45) per cent in non-invasive adenomas (p = 0.027); and 5.58 (7.24) per cent in cavernous sinus infiltrating v 2.10 (2.39) per cent in cavernous sinus non-infiltrating adenomas (p = 0.0005). To identify a value of labelling index beyond which adenomas should be considered invasive and another beyond which cavernous sinus infiltration should be suspected, normality Q-Q plots were obtained: a threshold labelling index of 3.5% for invasive adenomas and of 5% for cavernous sinus infiltrating adenomas was defined, with statistically significant differences (p = 0.02 and p = 0.004, respectively). Conclusions-The Ki-67 labelling index can be considered a useful marker in determining the invasive behaviour of anterior pituitary adenomas.