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European Journal of Histochemistry : EJH Mar 2019Vascular endothelial growth factor (VEGF), its inhibitory splice variant, VEGF165b and Endocrine Gland derived VEGF (EG-VEGF) have a controversial role in pituitary...
Vascular endothelial growth factor (VEGF), its inhibitory splice variant, VEGF165b and Endocrine Gland derived VEGF (EG-VEGF) have a controversial role in pituitary gland. We aim to study VEGF, VEGF165b and EG-VEGF expression in pituitary adenomas. A significant correlation was found between growth hormone (GH) and VEGF secretion (P=0.024). For prolactinomas, VEGF and prolactin expression, had a P-value of 0.02 for Kendall coefficient and a P-value of 0.043 for the Spearman coefficient. VEGF-mRNA amplification was detected in both tumor cells and folliculostellate cells. VEGF165b was positive in 16.66% of pituitary adenomas. EG-VEGF was significantly correlated with prolactin (P=0.025) and luteinizing hormone (P=0.028). Our data strongly support VEGF, VEGF165b and EG-VEGF as important players of pituitary adenomas tumorigenesis. Particular hormonal milieu heterogeneity, special vascular network with an unusual reactivity to tumor growth correlated with variability of VEGF, VEGF165b and EG-VEGF secretion may stratify pituitary adenomas in several molecular groups with a direct impact on therapy and prognosis.
Topics: Adenoma; Adenoma, Acidophil; Adenoma, Basophil; Adenoma, Chromophobe; Gene Expression Regulation; Humans; Immunohistochemistry; Pituitary Hormones; Pituitary Neoplasms; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor, Endocrine-Gland-Derived
PubMed: 30838843
DOI: 10.4081/ejh.2019.3010 -
Environmental Health Perspectives Jan 2003Dichloroacetic acid (DCA) is carcinogenic to the B6C3F(1) mouse and the F344 rat. Given the carcinogenic potential of DCA in rodent liver and the known concentrations of...
Dichloroacetic acid (DCA) is carcinogenic to the B6C3F(1) mouse and the F344 rat. Given the carcinogenic potential of DCA in rodent liver and the known concentrations of this compound in drinking water, reliable biologically based models to reduce the uncertainty of risk assessment for human exposure to DCA are needed. Development of such models requires identification and quantification of premalignant hepatic lesions, identification of the doses at which these lesions occur, and determination of the likelihood that these lesions will progress to cancer. In this study we determined the dose response of histopathologic changes occurring in the livers of mice exposed to DCA (0.05-3.5 g/L) for 26-100 weeks. Lesions were classified as foci of cellular alteration smaller than one liver lobule (altered hepatic foci; AHF), foci of cellular alteration larger than one liver lobule (large foci of cellular alteration; LFCA), adenomas (ADs), or carcinomas (CAs). Histopathologic analysis of 598 premalignant lesions revealed that (a)) each lesion class had a predominant phenotype; (b)) AHF, LFCA, and AD demonstrated neoplastic progression with time; and (c)) independent of DCA dose and length of exposure effects, some toxic/adaptive changes in non-involved liver were related to this neoplastic progression. A lesion sequence for carcinogenesis in male B6C3F(1) mouse liver has been proposed that will enable development of a biologically based mathematical model for DCA. Because all classes of premalignant lesions and CAs were found at both lower and higher doses, these data are consistent with the conclusion that nongenotoxic mechanisms, such as negative selection, are relevant to DCA carcinogenesis at lower doses where DCA genotoxicity has not been observed.
Topics: Adenoma, Acidophil; Adenoma, Basophil; Adenoma, Liver Cell; Animals; Carcinogenicity Tests; Dichloroacetic Acid; Dose-Response Relationship, Drug; Glycogen; Linear Models; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Necrosis; Rats; Rats, Inbred F344; Water Pollutants
PubMed: 12515679
DOI: 10.1289/ehp.5442 -
Molecular Pathology : MP Feb 2002In the pituitary gland, activating mutations of the GNAS1 (Gsalpha) gene at Gln227 have been identified in adrenocorticotrophin secreting, growth hormone secreting, and...
In the pituitary gland, activating mutations of the GNAS1 (Gsalpha) gene at Gln227 have been identified in adrenocorticotrophin secreting, growth hormone secreting, and prolactin secreting adenomas. To date, mutations at the codon encoding R201, typically underlying the McCune-Albright syndrome and isolated fibrous dysplasia of bone, have been demonstrated only in growth hormone secreting pituitary adenomas. In this study, a polymerase chain reaction amplified target sequence in exon 8 of the GNAS1 gene was sequenced, identifying the first R201 mutation seen in an isolated basophilic adenoma which generated Cushing's disease in a child. This case adds Cushing's disease to the range of human diseases caused by R201 mutations of the GNAS1 gene.
Topics: Adenoma, Basophil; Child; Cushing Syndrome; DNA Mutational Analysis; Female; GTP-Binding Protein alpha Subunits, Gs; Humans; Mutation, Missense; Oncogene Proteins; Pituitary Neoplasms
PubMed: 11836449
DOI: 10.1136/mp.55.1.58 -
Obesity Research Sep 1994
Topics: Adenoma, Basophil; Cushing Syndrome; Female; History, 20th Century; Humans; Obesity; Pituitary Neoplasms
PubMed: 16353601
DOI: 10.1002/j.1550-8528.1994.tb00097.x -
Endocrine Journal Oct 1993The patient was a 26-year-old man with Cushing's disease who underwent transsphenoidal microscopic surgery for a pituitary microadenoma. His postoperative course was...
The patient was a 26-year-old man with Cushing's disease who underwent transsphenoidal microscopic surgery for a pituitary microadenoma. His postoperative course was uneventful, but he died suddenly five years after the operation. At autopsy, a ruptured dissecting aneurysm with marked atherosclerosis was observed in the aorta. In the pituitary, a small focus of adrenocorticotropic hormone (ACTH) producing adenoma, possibly residual adenoma, was detected and Crooke's degeneration was observed in the non-tumorous pituitary gland. But immunohistochemical patterns of pituitary hormones in the non-tumorous pituitary gland were normal and the adrenal cortex was unremarkable. In the hypothalamus, corticotropin-releasing hormone immunoreactivity was not detected and arginine vasopressin was sporadically positive. Considering these findings, this patient may have developed subclinical hypercortisolism due to the residual adenoma at the time of autopsy, despite clinical remission. Cushing's syndrome is considered to be a risk factor dissecting aneurysm, and in this case the metabolic changes in Cushing's disease may have influenced the development of the dissecting aneurysm. Periodic cardiovascular re-evaluations should therefore be performed when there is clinical remission of Cushing's syndrome.
Topics: Adenoma, Basophil; Adrenocorticotropic Hormone; Adult; Aortic Dissection; Aortic Aneurysm; Aortic Rupture; Arginine Vasopressin; Arteriosclerosis; Corticotropin-Releasing Hormone; Cushing Syndrome; Death, Sudden; Fatal Outcome; Humans; Hypertension; Hypothalamo-Hypophyseal System; Hypothalamus; Male; Microsurgery; Neoplasm Recurrence, Local; Pituitary Gland, Anterior; Pituitary Neoplasms; Pituitary-Adrenal System; Postoperative Complications
PubMed: 7951528
DOI: 10.1507/endocrj.40.613 -
The American Journal of Pathology Sep 1991To study the relationship between null cell adenomas, oncocytomas and gonadotroph adenomas, we analyzed 32 surgically removed formalin-fixed paraffin-embedded pituitary...
To study the relationship between null cell adenomas, oncocytomas and gonadotroph adenomas, we analyzed 32 surgically removed formalin-fixed paraffin-embedded pituitary tumors for the expression of pituitary hormone messenger RNAs (mRNAs) by in situ hybridization (ISH). Most tumors were also analyzed for chromogranin A mRNA. To identify the cell type constituting the tumors and to assess hormone content, all tumors were investigated by histology, transmission electron microscopy and immunohistochemistry. Most null cell adenomas (6/11) and gonadotroph adenomas (9/10) expressed the mRNAs for alpha-subunit of glycoprotein hormones whereas only 2/11 oncocytomas expressed alpha-subunit mRNA. FSH beta and/or LH beta mRNA were present in most null cell and gonadotroph adenomas but only in a few oncocytomas. Prolactin (PRL) mRNA was detected in two null cell tumors and in one gonadotroph adenoma, whereas GH and POMC mRNA were present in one null cell adenoma. Chromogranin A mRNA, which codes for the major secretory granule protein, was present in 25/26 tumors including all tumors that were negative for pituitary hormone mRNAs, indicating adequate preservation of specific mRNA transcripts in the paraffin-embedded sections of tumor cells. These results indicate that null cell adenomas and gonadotroph adenomas are closely related neoplasms and that oncocytomas may represent a functionally defective form of null cell adenoma characterized by mitochondrial abundance, which has retained the capacity to synthesize the major secretory granule protein chromogranin A. Although the cytogenesis of null cell adenomas and oncocytomas is not clear, it can be suggested that these two tumor types are derived from a pluripotential precursor cell that is capable of undergoing multidirectional differentiation and synthesizing various hormones, mainly glycoproteins.
Topics: Adenoma; Adenoma, Basophil; Chromogranin A; Chromogranins; Humans; Nucleic Acid Hybridization; Pituitary Hormones; Pituitary Neoplasms; RNA, Messenger
PubMed: 1653518
DOI: No ID Found -
Neurologia Medico-chirurgica Oct 1989A case of pituitary apoplexy causing pituitary hemorrhage with extension into the third ventricle is reported. The patient was a 73-year-old, obese female admitted with...
A case of pituitary apoplexy causing pituitary hemorrhage with extension into the third ventricle is reported. The patient was a 73-year-old, obese female admitted with sudden onset of vomiting and impaired consciousness. Neurological examination revealed that she was stuporous, with marked neck stiffness and a dilated left pupil. A plain skull X-ray showed sellar enlargement and destruction of the dorsum sellae. Computed tomography demonstrated a high-density area in the third and lateral ventricles and a round, high-density mass in the suprasellar cistern. The patient died the next day. Autopsy revealed a large tumor in the sellar and suprasellar areas. The tumor and the hematoma within it compressed the floor of the third ventricle and passed through the lamina terminalis and the hypothalamic region. Histological examination disclosed a basophilic adenoma. The pituitary hemorrhage appeared to be the result of ischemia and necrosis within the pituitary adenoma caused by its acute expansion. The extension of the hematoma into the third ventricle was attributable to the large size of the tumor and its close adhesion to the floor of third ventricle.
Topics: Adenoma, Basophil; Aged; Cerebral Ventricles; Female; Humans; Pituitary Apoplexy; Pituitary Neoplasms
PubMed: 2482940
DOI: 10.2176/nmc.29.908 -
The American Journal of Pathology Dec 1984Thirty pituitary tumors, removed from 14 men and 15 women, were diagnosed as gonadotroph adenomas on the basis of their immunocytochemical and/or ultrastructural...
Thirty pituitary tumors, removed from 14 men and 15 women, were diagnosed as gonadotroph adenomas on the basis of their immunocytochemical and/or ultrastructural features. Serum follicle-stimulating hormone (FSH), but not luteinizing hormone (LH), was elevated in 8 men, whereas none of the women had gonadotropin levels, as measured by radioimmunoassay, inappropriately high for their age. Immunoreactive FSH (sometimes also LH) was present in 13 of 15 tumors in men but only 6 of 13 adenomas in women. By electron microscopy, gonadotroph adenomas in men had uncharacteristic features often similar to those of null-cell adenomas with poorly or moderately developed cytoplasmic organelles. In women, all tumors were well differentiated, with a highly distinctive vesicular dilatation of the Golgi complex ("honeycomb Golgi") as a diagnostic marker present in 14 of 15 adenomas. To the author's knowledge, this is the first example of sex-linked dichotomy within a tumor type expressed as the markedly different ultrastructural appearance of cytoplasmic organelles, especially the Golgi apparatus.
Topics: Adenoma; Adenoma, Basophil; Adenoma, Chromophobe; Adult; Aged; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Male; Middle Aged; Pituitary Gland, Anterior; Pituitary Neoplasms; Sex Characteristics
PubMed: 6095670
DOI: No ID Found -
The American Journal of Pathology Aug 1984Crooke's hyaline change was studied by immunocytochemistry using an anti-adrenocorticotropic hormone (ACTH) antiserum and five different antisera against cytokeratins....
Crooke's hyaline change was studied by immunocytochemistry using an anti-adrenocorticotropic hormone (ACTH) antiserum and five different antisera against cytokeratins. Crooke's hyaline appears in basophil cells of the adenohypophysis in patients with hypercortisolism, presumably as a part of the negative feedback on corticotropin secretion. Previous studies have identified the hyaline material as a simple protein, apparently unrelated to ACTH, and electron microscopy has revealed a loss of secretory granules and an accumulation of 6-9-nm filaments in the cytoplasm of affected cells. In this study, the secretory granules in adenohypophysial cells exhibiting Crooke's hyaline change were labeled by anti-ACTH antibodies, while the hyaline material was positive for cytokeratin with each of the five antisera used. The results suggest that high levels of glucocorticoids may stimulate elaboration of cytokeratins in basophils while they suppress the production and release of ACTH.
Topics: Adenoma, Basophil; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Aged; Cytoplasmic Granules; Cytoskeleton; Female; Humans; Hyalin; Immune Sera; Keratins; Male; Microscopy, Electron; Middle Aged; Pituitary Gland, Anterior; Pituitary Neoplasms
PubMed: 6205591
DOI: No ID Found -
Neurologia Medico-chirurgica Mar 1983
Topics: Adenoma, Basophil; Adult; Cerebral Hemorrhage; Cushing Syndrome; Female; Hematoma; Humans; Hypertension; Pituitary Neoplasms; Putamen
PubMed: 6193449
DOI: 10.2176/nmc.23.223