Maria Jaranowska

Immunocytochemical Investigations on the Vascularization of Pituitary Adenomas.

Blood vessels within pituitary adenomas were visualized using the immunocytochemical reaction for Factor VIII (von Willebrand Factor), a specific marker of the vascular endothelium. The number of immunopositive vascular profiles were counted and expressed as a mean number per one microscopic field. The results were related to the type of adenoma, established on the basis of immunocytochemical investigation using the antibodies against pituitary hormones or α-subunit (α-SU). It was found that the richest vascularization occurred in adenomas expressing follicle-stimulating hormone (FSH). The possible role of FSH in pituitary angiogenesis is discussed.

Immunohistochemical detection of FSH receptors in pituitary adenomas and adrenal tumors

Objectives . Follicle stimulating hormone (FSH) receptors (FSHR) are physiologically expressed in the ovary and testis. It is well known that FSHR are also expressed in gonadal cancers, but the data on their incidence in extra-gonadal tumors are scarce. Recently, the expression of FSHR in the vascular endothelium within different human cancers was found, but nothing is known on FSHR appearance in non-gonadal endocrine tumors. The present paper reports on the immunohistochemical detection of FSHR in human pituitary adenomas and adrenal tumors. Materials and methods . The study included samples of 28 pituitary adenomas and 36 adrenal tumors. Moreover, 2 samples of non-tumoral adrenal glands were also studied. FSH receptor immunostaining was performed on paraffin sections using the rabbit anti-human FSH-R polyclonal antibody raised against 1-190 amino acid sequence from the human FSH-R (sc-13935). The pituitary adenomas were immunostained to reveal the pituitary hormones and the proliferation marker Ki-67. Results . In the pituitary adenomas, positive immunostaining with anti-FSHR antibody occurred in the adenoma cells cytoplasm and endothelia of the intra- and peritumoral blood vessels. The cytoplasmic immunostaining was found in the majority of investigated tumors but the intensity of staining was weak to moderate. There is some tendency towards the higher cytoplasmic FSHR score in tumors with higher Ki-67 index (atypical adenomas). In contrast to the cytoplasm, the FSHR immunostaining in blood vessels is strong and concerns all the investigated samples. Strong FSHR immunostaining is present in the endothelium of intra- and/or peritumoral blood vessels in the majority of pheochromocytomas, approximatively one half of the adrenocortical adenomas and both cases of the adrenal cancers. The immunostaining is detectable also in the tumoral cell cytoplasm in all but one examined pheochromocytomas.. All the investigated adrenocortical adenomas presented strong immunostaining of cell membranes. No immunostained cell membranes were found. in adrenal cancers. The positive immunostaining was found in glandular cells, but not in blood vessels, of non-tumoral adrenal cortex and medulla. Conclusions . Immunostaining of FSHR often occurs in the endothelium of intra- and/or peritumoral blood vessels of pituitary adenomas and benign and malignant adrenal tumors. The immunostaining may be also present in tumoral cells. A role of FSHR expression in these tumors (stimulation of angiogenesis? stimulation of cell growth?) needs further studies to be clarified.

Ectopic expression of follicle-stimulating hormone receptors in thyroid tumors

Introduction In normal conditions follicle-stimulating hormone receptors (FSHR) are expressed in the ovary and the testis. They can also be expressed in gonadal tumors. However, recently we have found FSHR immunostaining in pituitary adenomas, adrenal tumors and neuroendocrine tumors (carcinoids). The aim of this study was to determine whether the same occurs in thyroid tumors. Material and methods Thirty-six samples of surgically excised thyroids were examined. Follicle-stimulating hormone receptors immunostaining was performed on paraffin sections using the rabbit anti-human FSHR polyclonal antibody raised against a 1-190 amino acid sequence from the human FSHR (sc-13935, Santa Cruz). Results Normal thyroid follicles do not show immunopositivity for FSHR. The same concerns the majority of benign lesions, diagnosed as hyperplasia nodularis or thyroid adenomas. However, positive FSHR immunostaining in some follicles was observed. In all but one thyroid cancer (15 papillary, 10 follicular cancers and one case of anaplastic thyroid cancer) 10–100% of tumor cells exhibit positive FSHR immunostaining. In about 40% of samples FSHR immunoreactivity can be observed also in the endothelia of intrathyroidal blood vessels. This immunopositivity was more frequent in the samples of thyroid cancers (13/27) than in benign lesions (2/9). Conclusions Ectopic positive FSHR immunostaining is also present in thyroid cancers, and, to a lesser degree, in benign lesions but not in the normal thyroid epithelium.

Overexpression of prothymosin alpha is related to pituitary adenoma recurrence but not to adenoma invasiveness and proliferation

INTRODUCTION Prothymosin alpha (ProTα) is a peptide initially considered as a thymic hormone, but further studies have shown its wide distribution in different tissues and organs. It has a prevalent nuclear localisation and is thought to be involved in the control of proliferation and apoptosis. In earlier studies, the overexpression of ProTα was found in several human tumours, including pituitary adenomas. The present study deals with the relations of ProTα to the pituitary adenoma hormonal phenotype, proliferation, recurrence and invasiveness. MATERIAL AND METHODS Sixty two pituitary adenomas were included in the study. The invasiveness of the tumours was estimated before surgery by means of magnetic resonance imaging. The paraffin sections of the tumours were immunostained with an antibody against the C-terminal fragment (101-109) of ProTα and with anti-Ki-67 antibody. The hormonal phenotype of the investigated pituitary adenomas had been established previously by means of immunostaining with antibodies to pituitary hormones (GH, PRL, FSH, LH, TSH, ACTH and α-subunit). RESULTS Strong immunostaining with anti-ProTα antibody occurred in the subpopulation of cell nuclei and the walls of intratumoural blood vessels. ProTα index is higher in clinically non-functioning pituitary adenomas (CNFPA) compared to any type of functioning adenomas. There was no difference in the percentage of ProTα- positive cell nuclei in non-invasive vs. invasive adenomas, but it was significantly more frequent in recurrent than in primary tumours. Moreover, the decrease of ProTα index was found in somatotroph tumours treated with somatostatin analogues vs. untreated ones. The percentage of ProTα nuclei did not correlate with Ki-67 index. CONCLUSIONS The overexpression of nuclear ProTα in pituitary adenomas is related to tumour recurrence, but not to proliferation or invasiveness.

Expression of follicle stimulating hormone receptors (FSHR) in thyroid tumours - a marker of malignancy?

BackgroundIn normal conditions FSHR are expressed in granulosa cells of the ovary and Sertoli cells of the testis. They can be expressed also in gonadal tumours. However, recently the expression of FSHR was found in tumoral cells and intra-tumoral blood vessels of many other tumours, including thyroid tumours. Aim of this study was to see whether the expression of FSHR can be useful in the differentiation of benign and malignant thyroid lesions.Methods44 samples of surgically excised thyroids were immunostained with anti- FSHR antibody raised against 1–190 amino acid sequence from the human FSHR.ResultsNon-neoplastic thyroid follicles (i.e. the follicles situated outside the tumour) do not show the immunostaining for FSHR. The same concerns the majority of follicular adenomas. In contrast, 87.5% of follicular cancers, the same percentage of papillary cancers and all the examined undifferentiated cancers showed the FSHR immunopositivity of tumoral cells. A tendency towards the higher frequency of FSHR – positive blood vessels also concerns malignant thyroid tumours.ConclusionsThe ectopic FSHR immunostaining seems to be useful to differentiate malignant from benign lesions, especially follicular cancers from follicular adenomas. However, the further studies on larger material are needed.

Expression of follicle stimulating hormone receptors in pituitary adenomas — a marker of tumour aggressiveness?

INTRODUCTION In our earlier study, we found that pituitary adenomas, like other human tumours, express ectopically follicle stimulating hormone receptors (FSHR) in intratumoural blood vessels endothelia and/or tumoural cells. The aim of the present paper was to provide more detailed data on FSHR expression in different subtypes of pituitary adenomas and to evaluate its possible role as a prognostic and/ or predictive biomarker in these tumours. MATERIAL AND METHODS Forty two pituitary adenomas, surgically removed, were immunostained with antibodies against the pituitary hormones, antigen Ki-67 and 1-190 fragment of FSHR. RESULTS The positive FSHR immunostaining was found in blood vessels endothelia of 88% of adenomas and in tumoural cells of 40% adenomas. In tumoural cells, the incidence of at least moderate FSHR immunostaining is significantly higher in invasive tumours (68%) compared to non-invasive (12%) ones, and higher (albeit not statistically significantly) in invasive-proliferating adenomas (Ki-67 > 3%, grade 2b) compared to invasive but non-proliferating (Ki-67 < 3%, grade 2a) ones. CONCLUSIONS The present study confirms that pituitary adenomas ectopically express FSHR in intratumoural blood vessels endothelia and tumoural cells. Moreover, the expression in tumoural cells is prevalent in invasive and proliferating adenomas vs. non-invasive and non-proliferating tumours.

Aberrant expression of follicle stimulating hormone receptors (FSHR) in thyroid neoplasia

In normal conditions FSHR are expressed in the ovary and the testis. It is well known that they can also be expressed in gonadal tumours. However, recently we have found FSHR immunopositivity in tumoral tissues of other endocrine tumours, namely pituitary adenomas, adrenal tumours and neuroendocrine gut and lung tumours (carcinoids). The aim of this study was to see whether the same phenomenon occurs in thyroid neoplasia.