Salehi, Fateme

Pituitary tumor transforming gene (PTTG) was initially found to be overexpressed in GH4 rat pituitary adenomas (PA). PTTG overexpression has been correlated with patient survival, tumor grade, and/or invasiveness in several tumors including those of thyroid, breast, lung, and colon. Studies of PTTG as a prognostic indicator in PAs are limited and show conflicting results. We investigated PTTG immunostaining in 79 PAs of different subtypes (growth hormone (GH), 12; prolactin (PRL), 6, adrenocorticotropic hormone (ACTH), 11, gonadotroph, 21; null cell, 29) in relation to clinico‐pathological variables including patient age and sex, as well as tumor size, and invasiveness. The streptavidin‐biotin‐peroxidase method was used, with a monoclonal PTTG antibody (Abcam, Cambridge, UK). PTTG expression was found to be cytoplasmic in all PAs, with highest levels being present in GH adenomas and lowest in the PRL ones. No correlation was found with patient age, sex, tumor size or invasiveness. Thus, it appears that PTTG cannot serve as a prognostic marker in patients with PAs. PTTG has been implicated in several tumorigenic processes including angiogenesis, DNA damage repair and invasiveness. PTTG overexpression in PA warrants further research into its role in PA initiation and progression.

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.

The aim of our work was to investigate immunohistochemical expression of nestin, a member of the intermediate filament family, in the adenohypophysial vasculature during the development and progression of pituitary infarction. Non‐tumorous adenohypopheses (45 cases) and pituitary adenomas (34 cases) of various types, all exhibiting acute or healing infarcts were examined. The streptavidin‐biotin‐peroxidase complex method was applied. In areas of adenohypophyses and pituitary adenomas with no infarction, nestin was expressed in scattered capillaries and endothelial cells. In acute infarcts, no nestin was demonstrable in the necrotic capillaries (50 cases). Where newly formed capillaries spread into necrotic zones, nestin expression was noted in all capillaries (25 cases). In the hypocellular, fibrotic scar phase, only few vessels were apparent and immunoreactivity was focal and mild (4 cases). In conclusion, nestin is strongly expressed in newly formed capillaries and is downregulated when infarcts transform to fibrous tissue. Nestin expression may provide valuable insight into the process of pituitary angiogenesis.

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.

Objective MGMT expression in brain and pituitary tumors has been correlated with temozolomide treatment. Few medical therapies are available in patients with Nelson Syndrome. The aim of the present study was to assess immunohistochemical expression of MGMT in ACTH‐secreting pituitary adenomas in patients with Nelson Syndrome. Methods Our material consisted of specimens from ACTH‐secreting pituitary adenomas from patients with Nelson Syndrome. Immunohistochemical staining for MGMT was performed using the streptavidin‐biotin‐peroxidase complex method. MGMT immunoreactivity was assessed microscopically and recorded as an estimated percentage of nuclear MGMT immunopositivity. (0=none, 1=<10%, 3=<50%, 4=>50%) Results Male:Female ratio was 3:5, with average patient age being 62 (range 57–66). Five of the eight specimens (65%) exhibited no MGMT immunoreactivity, with two out of eight cases (25%) showing slight MGMT immunopositivity and one out of eight cases (12%) demonstrating moderate MGMT immunopositivity (<25%). Conclusions Temozolomide therapy may be useful in patients with Nelson Syndrome. Absent or low MGMT staining in brain and other neoplasms has been shown to correlate with successful treatment with temozolomide, and recent reports assessing aggressive pituitary adenomas suggest similar outcome.

Following traumatic brain injury (TBI) approximately 25% of patients develop partial or complete hypopituitarism (HP). In our previous histologic study we found no changes in the pituitaries of patients who died instantly after TBI (Group I). In 43% of patients who survived 1‐7 days acute pituitary infarcts were apparent (Group II). In the present work, 3 group I and 7 group II pituitaries with infarcts were selected for histological and immunohistochemistry (IH) evaluation. IH was performed for adenohypophyseal hormones by the streptavidin‐biotin‐peroxidase method. In group I pituitaries, no histological changes were found and IH showed normal distribution and intensity for GH, PRL, ACTH, TSH, FSH, LH and α‐subunit (α‐SU). In group II pituitaries acute infarct (size range: 10% to 80%) was evident. IH in the non‐necrotic areas revealed no significant change. In the area of early necrosis the dying cells were still immunopositive (IP) for GH, PRL, ACTH, TSH, FSH, LS, and α‐SU. Even in the necrotic cells with loss of cell membrane, nuclear pyknosis, rhexis and lysis IP cytoplasms were still apparent indicating that hormone release is affected by ischemia. Subsequently the intensity of IP cells gradually decreased and IP granules leaked out from the necrotic cells and were seen extracellularly. In conclusion infarction and loss of adenohypophyseal cells may contribute to HP but other factors should also be considered.

Objective. We investigated the correlation between immunohistochemical expression of the pituitary tumor transforming gene (PTTG) and pituitary adenoma subtype. Methods. Pituitary adenomas (n = 89) were stained for PTTG using the streptavidin—biotin—peroxidase complex method and a monoclonal PTTG antibody. Results. PTTG staining was found to be cytoplasmic with a pronounced paranuclear expression pattern. Reactivity was highest in growth hormone (GH) adenomas as compared with other tumors, including prolactin (PRL), follicle-stimulating hormone/luteinizing hormone/α subunit, as well as adrenocorticotrophic hormone—secreting adenomas. PRL adenomas exhibited the lowest expression levels. Among GH adenomas, untreated tumors demonstrated significantly higher PTTG levels than octreotide-treated examples. Although dopamine agonist—treated PRL adenomas tended to show lower expression levels, statistical significance was not reached. Conclusions. Our finding that PTTG was differentially expressed in pituitary adenoma subtypes suggests a cell-specific function for PTTG. Moreover, treatment of GH adenomas with somatostatin analogues lowered PTTG expression. Further investigation into mechanisms mediating cell-specific expression of PTTG is warranted.

Object The aim of this work was to investigate the immunohistochemical expression of nestin, a member of the intermediate filament family, in adenohypophysial vasculature during development and progression of pituitary infarction. Methods Forty-five nontumorous adenohypophyses and 34 pituitary adenomas of various types, all exhibiting acute or healing infarcts, were examined immunohistochemically using the streptavidin-biotin-peroxidase complex method. Results In both adenohypophyses and pituitary adenomas without infarction, nestin was expressed in only a few capillaries and endothelial cells. In acute infarcts without a vascular response, no nestin was demonstrable within necrotic capillaries (50 cases). In organizing infarcts, newly formed vessels spreading into necrotic zones showed nestin expression in all capillaries and practically every endothelial cell (25 cases). In the hypocellular, fibrotic scar phase, only a few vessels (4) were apparent, and immunoreactivity was focal and mild. Conclusions Nestin is strongly expressed in newly formed capillaries and is downregulated when infarcts transform to fibrous tissue. Nestin expression may provide valuable insight into the process of pituitary angiogenesis.