1/8. Expression of vesicular monoamine transporters in endocrine hyperplasia and endocrine tumors of the oxyntic stomach.BACKGROUND: Gastric enterochromaffin-like (ECL) cells selectively express the vesicular monoamine transporter (VMAT) VMAT2, and enterochromaffin (EC) cells the VMAT1 isoform. Aims: We investigated whether VMAT isoform selection indicates the origin of endocrine hyperplasia and neoplasia from oxyntic ECL or EC cells and may be of prognostic significance in different types of gastric carcinoids. methods: Tissue from patients with chronic atrophic gastritis (CAG), Zollinger-Ellison-syndrome (ZES), gastric carcinoids and neuroendocrine carcinoma (NEC) was investigated by immunohistology and in situ hybridization. RESULTS: endocrine cells forming diffuse, linear, and micronodular hyperplasia in CAG and ZES, as well as oxyntic microcarcinoids expressed both VMAT2 and chromogranin a (CgA) but neither VMAT1 nor serotonin. In five of six sporadic carcinoids VMAT2 and CgA but not VMAT1 were detected. One carcinoid was copositive for VMAT1 and serotonin but negative for VMAT2. Electron microscopy confirmed the VMAT2-positive tumors as ECLoma and the VMAT1-immunoreactive carcinoid as EComa. CONCLUSIONS: VMAT2 and VMAT1 are reliable markers for differentiation of gastric endocrine hyperplasia and neoplasia from ECL and EC cells, respectively. The significance of VMAT2 and VMAT1 as prognostic markers lies in the relatively poor prognosis for EComa compared to ECLoma, characterized by VMAT2 positivity. The absence of both VMAT2 and VMAT1 in NEC may indicate poor prognosis.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/8. Primary carcinoid tumor of the testis: Immunohistochemical, ultrastructural and FISH analysis with review of the literature.Primary carcinoid tumor of the testis only accounts for 0.2% of all carcinoid tumors in japan. The clinicopathological features, including differences between Japanese and europe/united states (Eur/US) series', which are known in ovarian carcinoids, have not yet been sufficiently recognized. In the present study, five testicular carcinoids from various clinicopathological viewpoints were analyzed, with a review of the literature. All 15 cases in japan, including 10 previously reported, were insular carcinoids. Three of the 15 cases (20%) were associated with a teratoma. serotonin production was confirmed in at least 10 cases (five cases in the present study and five cases in previous studies), but carcinoid syndrome was present in only two cases. Three of the 15 cases (20%) showed distant metastases, and the tumors that metastasized were larger than those that did not. These features were almost similar to those observed in the Eur/US series. Three pure carcinoids were also studied for the number of sex chromosomes by fluorescence in situ hybridization (FISH). They did not show a significant numerical abnormality of the X chromosome, which is common in testicular germ cell tumors. Therefore, the genetic background of pure carcinoids might be different from that of common germ cell tumors.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/8. A case of Epstein-Barr Virus (EBV)-associated thymic carcinoid and investigation of existence of EBV-infected cells in thymus and thymic tumors.We describe the first case of Epstein-Barr virus (EBV)-associated thymic carcinoid tumor found by in situ hybridization (ISH) on paraffin-embedded sections. ISH revealed that both tumor cells and infiltrated lymphocytes were EBV positive, while a few EBV-infected lymphocytes were detected in 2 of 11 thymuses and 1 of 11 thymomas.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/8. Large cell neuroendocrine carcinoma of the uterine cervix with cytogenetic analysis by comparative genomic hybridization: a case study.Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a newly introduced category of the revised world health organization classification. We reported a case of cervical LCNEC with cytogenetic analysis by comparative genomic hybridization (CGH). The cervical tumor showed moderately increased mitotic activity (8-14 mitotic figures per 10 high-power fields) and focal necrosis, which made it problematic to differentiate from atypical carcinoid. CGH analysis failed to detect chromosome 11q loss that has been reported to be characteristic of pulmonary atypical carcinoids. Furthermore, chromosome 3q amplification, which has been detected frequently in pulmonary small cell carcinomas and LCNECs but not in pulmonary typical and atypical carcinoids, was the most remarkable chromosomal aberration. Although CGH reports are extremely rare in neuroendocrine tumors of the uterine cervix, specific chromosomal aberrations may be useful in their distinction.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
5/8. Characterization of the somatostatin receptor subtype in a bronchial carcinoid tumor responsible for Cushing's syndrome.Small ACTH-secreting carcinoid tumors responsible for Cushing's syndrome are often difficult to localize using available radiological investigations. somatostatin receptors have been found in about 90% of carcinoid tumors studied, leading to a new approach for the localization of tumors or metastasis by using radiolabeled somatostatin analogs. We report a case of Cushing's syndrome due to an ACTH-secreting bronchial carcinoid tumor, completely suppressible with octreotide treatment and evidenced by body scintigraphy with 111In-labeled pentreotide. After removal, which led to patient recovery, the tumor was studied in vitro. in situ hybridization, using a complementary dna probe, revealed POMC messenger ribonucleic acid in a subpopulation of tumor cells. These cells were labeled by immunochemistry using an antiserum directed against ACTH. Confocal laser scanning microscopy analysis showed that the ACTH-immunoreactive peptide was sequestered in secretory granules. Autoradiographic labeling using [125I-Tyrzero,D-Trp8]somatostatin-14 demonstrated the presence of somatostatin-binding sites in the whole tumor tissue. The relative affinities of various selective somatostatin analogs and the ability of GTP to inhibit radioligand binding suggested that the receptor expressed in the tumor cells belonged to the SSTR-2 subtype.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/8. Somatotroph hyperplasia without pituitary adenoma associated with a long standing growth hormone-releasing hormone-producing bronchial carcinoid.acromegaly is most often associated with a pituitary somatotroph adenoma. While multiple lines of evidence suggest an intrinsic somatic cell defect in adenoma formation, the role of hypothalamic hormones in pituitary tumorigenesis remains unclear. We describe the functional and morphological features of the pituitary of a patient with a long-standing ectopic GH-releasing hormone (GHRH)-producing tumor and acromegaly. This 28-yr-old woman with a documented 10-yr history of a disseminated bronchial carcinoid was evaluated for clinical features of acromegaly. Elevated serum GH (88 micrograms/L) was not suppressed after glucose ingestion and was paradoxically stimulated by TRH, but did not respond to GHRH or GnRH administration. serum insulin-like growth factor-1 (730 micrograms/L; normal, < 333 micrograms/L), insulin-like growth factor-binding protein-3 (9.5 mg/L; normal, 2-4.2 mg/L), and GHRH (26.1 micrograms/L; normal, < 20 ng/L) were elevated. magnetic resonance imaging revealed a diffusely enlarged pituitary gland. octreotide treatment for 4 months resulted in suboptimal clinical and biochemical responses. Examination of the transsphenoidally resected pituitary by light microscopy revealed diffuse somatotroph hyperplasia, with intact reticulin network and preservation of the acinar architecture. Electron microscopy showed active somatotrophs interspersed with other cell types. in situ hybridization revealed very strong positivity for GH mRNA, whereas fewer cells contained GHRH and somatostatin mRNA signals. Dispersed pituitary cells secreted GH into culture medium. GH release was stimulated by GHRH and GHRH plus TRH, but not by TRH alone; GH was suppressed by octreotide in vitro. We conclude that sustained exposure to ectopic GHRH leads to somatotroph hyperplasia, but, at least in this case, was not sufficient for adenomatous transformation.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/8. Expression of prohormone convertase, PC2, in adrenocorticotropin-producing thymic carcinoid with elevated plasma corticotropin-releasing hormone.An autopsy case of ACTH-producing thymic carcinoid with Cushing's syndrome is reported. The patient was a 63-yr-old man with multiple bone metastases from an undetermined primary site. hyperpigmentation was observed at the terminal stage. The plasma levels of ACTH, cortisol, chromogranin a, and urinary 17-hydroxy-corticosteroids were extremely high, and ectopic ACTH-producing neuroendocrine tumor was diagnosed. In addition, plasma CRH was high. autopsy revealed that the patient had primary thymic carcinoid with extensive metastases. Remarkable hyperplasia of the adrenal cortexes and Crooke's hyaline degeneration of the pituitary gland were consistent with Cushing's syndrome by ectopic ACTH production. There were multiple CRH-producing cells without degenerative changes in the hypothalamus. The tumor cells were immunoreactive to ACTH, CRH, and the cleavage enzyme PC2. POMC messenger ribonucleic acid and PC2 messenger ribonucleic acid were detected in the tumor cells by an in situ hybridization method. Expression of PC2 was considered to induce hyperpigmentation by producing alpha MSH. Despite hypercortisolism and ectopic production of CRH by the tumor cells, hypothalamic CRH cells were not atrophic. This case is a good example to demonstrate the correlation between CRH and the hypothalamo-pituitary-adrenal axis as well as hyperpigmentation in Cushing's syndrome.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/8. Typical and atypical carcinoid tumors of the lung are characterized by 11q deletions as detected by comparative genomic hybridization.neuroendocrine tumors of the lung represent a wide spectrum of phenotypically distinct entities with different biological characteristics such as typical carcinoid tumor (TC), atypical carcinoid tumor (AC), large-cell neuroendocrine carcinoma (LCNEC), and small-cell lung carcinoma (SCLC). The histogenetic relationships between TC, AC, LCNEC, and SCLC are still unclear. This study was carried out to provide cytogenetic data about pulmonary neuroendocrine tumors and to evaluate their characteristic alterations and histogenetic relations for an improved understanding of the mechanisms of tumor development. Twenty-nine paraffin-embedded tumor samples of TC (n = 17), AC (n = 6), LCNEC (n = 3), and SCLC (n = 3) were selected for isolation of tumor dna and subsequent comparative genomic hybridization (CGH) analysis. To confirm the comparative genomic hybridization results for characteristic chromosomal imbalances, selected cases were additionally investigated by loss of heterozygosity analysis. For statistical evaluation, we also used comparative genomic hybridization data from 45 published SCLC cases. dna underrepresentations of 11q were the most frequent findings in TC (8 of 17) and AC (4 of 6), whereas these aberrations were rare in LCNEC (1 of 3) and SCLC (0 of 3). Furthermore, AC showed dna underrepresentation of 10q (3 of 6) and 13q (3 of 6). In contrast, SCLC and LCNEC were characterized by a different pattern of dna losses (3p-, 4q-, 5q-, 13q-, and 15q-) and gains (5p , 17p , and 20). Statistical analysis revealed significantly different occurrences of 11q deletions in TC/AC versus SCLC (45 published cases of SCLC and our 3 cases; P = 0.002; Fisher's exact test). Thus, TC and AC display frequent loss of 11q material including the MEN1 gene locus, which represents a characteristic genetic alteration in these tumors. Losses of 10q and 13q sequences allow a further cytogenetic differentiation between TC and AC. These additional changes might be responsible for the more aggressive behavior of AC. Three cases of LCNEC, the first to be analyzed by comparative genomic hybridization, exhibited similar complex abnormal patterns (4q-, 5q-, 10q-, 13q-, 15q-) to those of SCLC. Although neuroendocrine tumors of the lung share common phenotypic features, suggesting a genotypic relationship, they differ remarkably in their cytogenetic characteristics, highlighting an early fundamental molecular divergence during the development of these tumors.- - - - - - - - - - ranking = 8keywords = hybridization (Clic here for more details about this article) |