Last update:
28-Jul-2000

Arch Hellen Med, 16(6), November-December 1999, 580�589

ORIGINAL PAPER

Correlation of bcl-2 and bax protein expression with apoptosis
in human pituitary adenomas

D. SAMBAZIOTIS,¹ G. KONTOGEORGOS,¹ N. KAPRANOS^2
1Department of Pathology �Georgios Gennimatas� General Hospital,
²Department of Molecular Pathology, �Amalia Fleming� Hospital, Athens, Greece

OBJECTIVE The bcl-2 oncogene and the bax gene and their protein products play an important role in the regulation of apoptosis. The aim of the study was to investigate the effects of bcl-2 and bax proteins and their relation with apoptosis in a series of 81 pituitary adenomas
METHOD The 60 functioning adenomas included 19 somatotroph, 16 lactotroph, 10 mixed somatotroph-lactotroph and 15 corticotroph adenomas. The remaining 21 cases were clinically nonfunctioning adenomas. Bcl-2 and bax proteins were studied immunohistochemically and the results were quantitated with the use of the Histoscore system (HSC), by multiplying the immunoreactivity grade (1�4) with the staining intensity grade (1�3). Apoptotic cells were detected by the in situ end labeling technique (ISEL) on paraffin sections and the apoptotic labeling index (ALI) was accessed.
RESULTS Bcl-2 protein immunopositivity was found in 58% of the tumors, including 32 (53.5%) functioning and 15 (71.5%) nonfunctioning adenomas. Bax protein was found to be immunoreactive in 65 tumors (80%), including 50 (83.5%) functioning and 15 (71.5%) nonfunctioning adenomas. Bcl-2 HSC was significantly higher (P=0.02) in nonfunctioning (4.95) than in functioning (2.76) adenomas. Regarding bax HSC, no statistically significant differences were found between functioning (5.91) and nonfunctioning (5.58) adenomas. Overall, 45 of 81 (55.5%) adenomas included positive apoptotic nuclei by the ISEL technique. Functioning adenomas showed a significantly higher (P=0.03) ALI (5.7%) than that of nonfunctioning tumors (1.92%). The highest frequency of positive nuclei was noticed in corticotroph adenomas (6.81%), followed by lactotroph (5.57%), somatotroph (5.51%) and mixed somatotroph-lactotroph (4.59%) tumors. An inverse correlation was found between ALI and bcl-2 protein expression in almost all adenoma types. These differences were statistically significant only in corticotroph adenomas (P=0.02). In contrast, the apoptotic rate showed no correlation with bax protein expression.
CONCLUSIONS Apoptosis occurs mainly in functioning adenomas, with a statistically significant differences from nonfunctioning tumors. Bcl-2 protein expression is lower as compared to bax protein. In addition, it is significantly higher in nonfunctioning adenomas and shows inverse correlation with ALI. These results show that bcl-2/bax heterodimer is implicated in the regulation of the apoptotic process in human pituitary adenomas.

Key words: Apoptosis, bcl-2, bax, Pituitary adenoma.