ABSTRACT
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.
Subject(s)
Adenoma/metabolism , Pituitary Hormones/analysis , Pituitary Neoplasms/metabolism , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor, Endocrine-Gland-Derived/metabolism , Adenoma/genetics , Adenoma/pathology , Adenoma, Acidophil/genetics , Adenoma, Acidophil/metabolism , Adenoma, Acidophil/pathology , Adenoma, Basophil/genetics , Adenoma, Basophil/metabolism , Adenoma, Basophil/pathology , Adenoma, Chromophobe/genetics , Adenoma, Chromophobe/metabolism , Adenoma, Chromophobe/pathology , Gene Expression Regulation , Humans , Immunohistochemistry , Pituitary Neoplasms/genetics , Pituitary Neoplasms/pathology , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor, Endocrine-Gland-Derived/geneticsABSTRACT
BACKGROUND: Mutations of the genes encoding the alpha subunit of the stimulatory G protein (Gs) and of the inhibiting Gi2 protein (GNAS1 and GNAI2 genes, respectively) have been described in various endocrine neoplasias, including pituitary tumors. AIM: To search for mutations of GNAS1 and GNAI2 in a continuous series of non-functioning pituitary adenoma (NFPA) patients neurosurgically treated. SUBJECTS AND METHODS: The surgical samples of 22 patients who have been defined and characterized on a clinical, biochemical, histological, and immunohistochemical point of view have been processed for investigating the presence of the above mutations by PCR amplification of the hot spots exons 8 and 9 of GNAS1, and exons 5 and 6 of GNAI2, followed by direct sequencing. Moreover, the promoter region of GNAI2, in order to assess the prevalence of single nucleotide polymorphisms (SNP), was investigated in the same series. RESULTS: A CGT>TGT mutation at codon 201 of GNAS1 gene in a single case of NFPA was found, but no mutation of GNAI2A was demonstrated. CONCLUSIONS: This finding suggests and confirms that G-protein mutations are rare and not crucial in NFPA development. Additionally, we found a silent SNP at codon 318 in the promoter of the Gi2alpha gene in one out of the 22 NFPA.
Subject(s)
Adenoma, Acidophil/genetics , Adenoma, Chromophobe/genetics , GTP-Binding Protein alpha Subunits, Gs/genetics , Intracellular Signaling Peptides and Proteins/genetics , Pituitary Neoplasms/genetics , Adult , Aged , Chromogranins , Codon/genetics , Exons , Female , Humans , Male , Middle Aged , Mutation , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Repressor ProteinsABSTRACT
OBJECTIVE: To investigate the degree of malignancy and the biological behavior of small renal tumors and provide a pathological basis for clinicians in determination of further treatment and prognosis. METHODS: Flow cytometry and immunohistochemical studies were performed on 48 small tumors with diameters less than 3 cm. and 39 renal cell carcinomas with diameters larger than 3 cm in comparison to assess their DNA ploidy status and Ki-67 PR (proliferation rate). RESULTS: Of the 48 small renal tumors, 6 adenoma were all diploid with low PR (< 1%). Aneuploid rate of 42 small renal tumors with clear and granular cell type was 16.7%, showing no statistical difference with the 33.3% aneuploid rate of 39 large renal cell carcinomas. 42 small renal tumors had a lower mean PR than large renal cell carcinoma. DNA ploidy correlated closely with nuclear grade, stage and histological type. There existed a close relation between PR and grade. CONCLUSION: Small renal tumors consist of both adenoma and carcinoma, therefore tumor size can not be used as a criterion in their differential diagnosis. DNA ploidy and Ki-67 PR are important indicators for predicting the biological behavior and prognosis of renal parenchymal tumors.
Subject(s)
Adenocarcinoma, Clear Cell , Adenocarcinoma, Clear Cell/pathology , Adenoma, Acidophil , Adenoma, Acidophil/pathology , DNA, Neoplasm/genetics , Ki-67 Antigen/metabolism , Kidney Neoplasms/pathology , Adenocarcinoma, Clear Cell/genetics , Adenocarcinoma, Clear Cell/metabolism , Adenoma, Acidophil/genetics , Adenoma, Acidophil/metabolism , Aneuploidy , Diagnosis, Differential , Diploidy , Female , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , MaleABSTRACT
We report two cases of acromegaly due to pituitary adenoma without any other endocrinopathy in a family. The patients had high plasma GH and were improved by transsphenoidal adenomectomy. Acromegaly is usually a clinical syndrome of sporadic nonfamilial occurrence. The familial occurrence of acromegaly not associated with multiple endocrine neoplasia is very rare. Our patients are unlikely to be associated with the multiple endocrine neoplasia type 1 syndrome. Here we describe two patients with acromegaly, a father and his daughter, and review familial cases reported.
Subject(s)
Acromegaly/genetics , Adenoma, Acidophil/genetics , Adenoma, Chromophobe/genetics , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Endocrine Neoplasia/genetics , Pedigree , Pituitary Neoplasms/geneticsABSTRACT
The authors report four cases of familial pituitary adenomas from two unrelated families. No clinical or biochemical evidence of multiple endocrine neoplasia, type I (MEN-I) was demonstrated. Detailed study of the family trees disclosed no other family members affected by MEN-I. Familial occurrence of pituitary adenomas unassociated with MEN-I is rare.
