Kovács, Kálmán

Estrogen is involved in pituitary tumorigenesis, acting through estrogen receptors alpha (ERα) and beta (ERβ). Our study investigated the prognostic value of ERα/ERβ as markers in pituitary adenomas. Tissue samples and clinico‐pathological data (patient age and sex, tumor size, invasiveness and recurrence) were obtained from 78 patients with pituitary adenomas. Immunohistochemistry was performed using the streptavidin‐biotin‐peroxidase complex method. A monoclonal and polyclonal antibody were used for ERα and ERβ expression respectively. Intensity of ERα/ERβ expression was evaluated using a scale of 0 to 3. Percentage of positive cells was evaluated on a scale of 0 to 4. ERα immunopositivity was evident in 40 of 78 cases (51%), while ERβ stained positive in 49 of 78 cases (63%). No correlation was found between ERβ expression and pituitary tumor cell types or clinico‐pathological factors. A significant difference was present in ERα expression between different tumor types. ERα positivity was present to a greater extent in macroadenomas. This finding supports the role of ERα in tumor growth and progression. Elevated ERα positivity and intensity were also found in non‐invasive adenomas. It appears that ERα may be a valuable biological marker for tumor size and invasiveness, while ERβ is a poor marker. The role of ERα expression in pituitary tumor initiation and progression warrants further investigation.

Pituitary tumor transforming gene (PTTG) plays a role in many cellular processes. PTTG overexpression is seen in several tumor types and correlates with survival time/recurrence. We evaluated PTTG expression in various types of brain tumors (n=94). Immunohistochemistry was performed using a monoclonal PTTG antibody (DCS‐280, Abcam;Cambridge, MA) and the streptavidin‐biotin‐peroxidase complex method. The intensity of PTTG immunoreactivity was evaluated semi‐quantitatively on a 0‐4 scale. PTTG expression was evident in most tumor cells and was predominantly nuclear. In glial tumors, PTTG immunoreactivity was higher in glioblastomas (IV), anaplastic oligoastrocytomas (III), anaplastic oligodendrogliomas (III), oligoastrocytomas (II), oligodendrogliomas (II), and pilocytic astrocytomas (I) (range: 3.1–3.5), whereas notably lower PTTG was seen in myxopapillary ependymomas (I) and ependymomas (II) (1.5 & 1.6). In non‐glial tumors, hemangiopericytomas and schwannomas had higher PTTG score (3.4), than meningiomas (2.3). Thus, it appears that PTTG expression is not associated with tumor grade, but rather with tumor type, the most striking difference being between ependymomas and other glial tumors. PTTG may be a valuable therapy target in some brain tumors. Acknowledgments Authors thank the Jarislowsky Foundation and the Lloyd‐Carr‐Harris Foundation for their generous support.

Pituitary enlargement, development of pregnancy cells and prolactin cell hyperplasia are known to occur in pregnancy. In the present work, we assessed microvessel densities in the 20 pituitaries of pregnant women who passed away. Twenty pituitaries of age matched non‐pregnant women who died from non‐endocrine diseases were used as controls. The autopsy obtained pituitaries were formalin fixed and paraffin embedded. Slides were immunostained for adenohypophysial hormones and for CD‐34, an endothelial cell biomarker using the streptavidin‐biotin‐ peroxidase complex method. Microvessel densities were evaluated quantitatively in 10 random high‐ power fields. For statistical analysis, the chi‐square and Fisher exact tests were applied. The results confirmed that the pituitaries of pregnant women increased in weight and contained more PRL immunopositive cells compared to the controls. The formation of pregnancy cells was also evident. In the pituitaries of pregnant women compared to the control, microvessel densities were significantly higher. The cause of increased vascularity remains to be evaluated. This work was supported by the Jarislowsky and Lloyd Carr‐Harris Foundations.

Angiogenesis is a crucial event in tumor growth, invasion and development of metastasis. Endoglin (CD‐105), a disulfide‐linked homodimeric cell membrane glycoprotein of 180 kDa, located on chromosome 9q and binds to several components of the TGF beta family. In contrast to other endothelial cell markers, endoglin can be demonstrated only in proliferating endothelial cells. We investigated endoglin immunoexpression in various surgically removed human pituitary tumor types and compared the results with CD‐34 immunoexpression. For immunohistochemistry, the streptavidin‐biotin‐peroxidase complex method was used and the number of vessels were counted in 10 low power fields. Results show that endoglin immunostains fewer vessels than CD‐34 in every pituitary adenoma type. The number of endoglin immunopositive vessels is highest in untreated prolactinomas and subtype 3 silent pituitary adenomas and lowest in subtype 1 silent corticotroph adenomas and GH adenomas exposed to somatostatin analogs and prolactinomas exposed to dopamine agonists. Our findings are consistent with the view that endoglin is upregulated in proliferating endothelial cells and its expression can be used as an indicator of vascular neoformation in pituitary tumors. The low levels of endoglin expression in pituitary tumors exposed to somatostatin or dopamine agonists suggests that these therapeutic drugs can inhibit angiogenesis.

SNAP‐25, a synaptosome associated exocytosis protein of 25 kDa plays an important role in the secretory activity of several endocrine cells. In the present study, we investigated 15 PRL, 10 GH, 5 ACTH, 5 TSH, 15 FSH/LH/ alpha subunit producing, and 5 null cell adenomas. Surgically removed, formalin‐fixed and paraffin embedded human pituitary tumors were used. Sections were immunostained by the streptavidin‐biotin‐peroxidase complex method. The results showed that 10 PRL producing adenomas were strongly immunoreactive for SNAP‐25. The immunopositive material was located mainly on the plasmalemma. The nuclei were immunonegative, the cytoplasm was mildly immunopositive in several cells. Treatment of patients with dopamine agonists before surgery decreased markedly SNAP‐25 immunopositivity in 5/10 cases. In GH producing adenomas SNAP‐25 was seen in 5 cases. Immunopositivity was mild‐ moderate, membrane bound and cytoplasmic. Somatostatin analogs caused no marked reduction in immunopositivity (5 cases). Other adenoma types were practically immunonegative. Among human pituitary adenomas only PRL producing tumors release their secretory granules via exocytosis as was demonstrated by electron microscopy. This observation is concordant with our results. In dopamine agonist treated patients, decreased SNAP‐25 expression in PRL producing adenoma cells is consistent with reduction of blood PRL levels.