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.