Immunohistochemical Analyses of Cell Cycle-related Proteins, Apoptosis, and Proliferation in Pituitary AdenomasHiromichi Nakabayashia, Ichiro Sunadaa, and Mitsuhiro Haraba Department of Neurosurgery, Saiseikai Ibaraki Hospital, Osaka, Japan b Department of Neurosurgery, Osaka City University Medical School, Osaka, Japan Correspondence to: Hiromichi Nakabayashi, Dept. of Neurosurgery, Saiseikai Ibaraki Hospital, 1-1-24 Mitsukeyama, Ibaraki, Osaka K 573-0701, Japan. E-mail: nakabayashi@kcat.zaq.ne.jp To analyze the cell cycle regulatory mechanisms in the growth of pituitary adenomas, we investigated immunohistochemically the expression of the cell cycle-related proteins cyclin A and p27 in 48 pituitary adenomas. The frequency of apoptosis and the proliferative potential were also examined. The percentage of apoptotic cells was evaluated by immunohistochemical analysis using the anti-single-strand DNA antibody. The proliferative potential was assessed using the anti-Ki-67 antibody. The mean cyclin A labeling index (LI) for the non-recurrent group was 1.03% and for the recurrent group 2.31%. A positive linear correlation between cyclin A LI and Ki-67 LI was found. The mean p27 LI for the non-recurrent group was 67.4% and for the recurrent group 47.0%. There were significant differences in cyclin A LI and p27 LI between the non-recurrent group and the recurrent group. The mean apoptotic rate for the non-recurrent group was 0.87% and for the recurrent group 1.05%. There was no significant difference. Multivariate regression analysis revealed that high cyclin A LI and high Ki-67 LI were significant factors for shorter progression-free survival. The results suggest that the cyclin A LI is a useful prognostic factor in pituitary adenomas. (J Histochem Cytochem 49:11931194, 2001) Key Words: cyclin A, p27, single-strand DNA, apoptosis, pituitary adenoma
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