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(American Journal of Pathology. 2000;156:245-251.)
© 2000 American Society for Investigative Pathology

Regular Articles

Determination of the Proliferation and Apoptotic Index in Adrenocorticotropin-Secreting Pituitary Tumors

Comparison between Micro- and Macroadenomas

Marco Losa*, Raffaella L. A. Barzaghi*, Pietro Mortini*, Alberto Franzin*, Francesca Mangili{dagger}, Maria Rosa Terreni{dagger} and Massimo Giovanelli*

From the Pituitary Unit of the Department of Neurosurgery*
and the Department of Pathology,{dagger}
IRCCS San Raffaele, University of Milano, Milano, Italy

We investigated the growth fraction and cell loss fraction in a large group of patients with Cushing’s disease subdivided according to tumor size. Fifty-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 and the remaining 15 a macroadenoma. Immunohistochemical analysis was performed on paraffin-embedded material using a monoclonal antibody (MIB-1) directed against a proliferation-associated nuclear antigen, Ki-67, to measure the growth fraction. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method, using a monoclonal antibody recognizing areas of DNA fragmentation. Ki-67 labeling index and apoptosis were counted on separate slides in at least 1000 evaluable cells. Patients 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), whereas 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 study shows that ACTH-secreting macroadenomas are characterized by a higher cell growth fraction than microadenomas, whereas the cell loss fraction is not different. A high proliferation rate seems to play a major role in determining the progression from small to large pituitary tumors in Cushing’s disease.




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