Determination of the proliferation and apoptotic index in adrenocorticotropin-secreting pituitary tumors - Comparison between micro- and macroadenomas

We investigated the growth fraction and cell loss fraction in a large group of patients with Gushing's disease subdivided according to tumor size. Fif ty-one patients, 8 males and 43 females, aged 12 through 61 years (mean age 34.6 +/- 1.5 years),were studied, Thirty-six patients had a microadenoma a nd the remaining 15 a macroadenoma. Immunohistochemical analysis was perfor med on paraffm-embedded material using a monoclonal antibody (MIB-1) direct ed against a proliferation-associated nuclear antigen, Ki-67, to measure th e growth fraction, Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method, using a monoclonal anti body recognizing areas of DNA fragmentation. Ki-67 labeling index and apopt osis were counted on separate slides in at least 1000 evaluable cells, Pati ents with a macroadenoma had a significantly higher value of Ki-67 index (9 .3 +/- 2.7%) than patients with microadenoma (2.8 +/- 0.5%; P < 0.002),wher eas the apoptotic index was not significantly different in the two groups ( 1.7 +/- 0.8% in macroadenomas versus 0.8 +/- 0.3% in microadenomas), Our st udy shows that ACTH-secreting macroadenomas are characterized by a higher c ell growth fraction than microadenomas, whereas the cell loss fraction is n ot different. A high proliferation rate seems to play a major role in deter mining the progression from small to large pituitary tumors in Gushing's di sease.