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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene for multiple endocrine neoplasia type 1 (MEN1), an inherited predisposition to neuroendocrine neoplasm of the parathyroid glands, the pancreatic islet parenchyma, and the anterior pituitary gland, was recently mapped to chromosome 11q13 based on genetic linkage in families. We now show that the pathogenesis of MEN1-associated parathyroid lesions involves unmasking of a recessive mutation at the disease locus and that sporadic primary hyperparathyroidism shares the same mechanisms. By examination of allele losses in MEN1-associated lesions, we could define deletions of chromosome 11 and map the MEN1 locus to a small region within chromosome band 11q13, telomeric to the PYGM locus. In contrast, a low incidence of deletions involving the MEN1 gene was found in sporadic pituitary adenomas.
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PMID:Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors. 196 41

We review here the 10-year experience at the University of Michigan with 35 patients with gastrin hypersecretion who underwent transhepatic venous sampling (THVS) for tumor localization. Since 1978 THVS has been done routinely in all patients with gastrinoma syndrome considered for operation. Thirty-one patients had proved gastrinomas--21 benign sporadic tumors and 10 tumors associated with multiple endocrine neoplasia type-I (MEN I) syndrome. The correlation between the site of the maximal gradient and location of a sporadic tumor was poor. Overall sensitivity was only 35%, specificity 89%, and negative predictive value 89%. If gradients were regionalized to three areas--body and tail, gastrinoma triangle, and hepatic lobes--then sensitivity was 94%, positive predictive value 94%, and specificity 97%, with a negative predictive value of 97%. The maximal gastrin gradient above the mean for other values gave the greatest sensitivity and specificity. In MEN I syndrome, only four of eight patients with macroadenomas had their tumors correctly localized, a sensitivity of 50% and specificity and negative predictive value of 75%. In 19 patients who had operative localization of sporadic gastrinoma, computed tomography had a sensitivity of 31%, specificity of 66%, positive predictive value of 83%, and negative predictive value of 15%. Selective angiography was better, with a sensitivity of 29%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 100%. Regionalization to the triangle proved valuable for detection of microgastrinomas, as was measurement of hepatic vein gastrins for identification of intrahepatic tumors. In MEN I syndrome, if regionalization was achieved (50%), tumor resection appeared to offer hope of "cure." We conclude that THVS is the best tool for tumor regionalization to the pancreatic tail and body, gastrinoma triangle, and hepatic lobes. It has allowed us to achieve surgical cure in 19 of 21 patients with sporadic gastrinomas and improvement in four of eight patients with MEN I syndrome.
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PMID:Transhepatic portal vein catheterization for localization of sporadic and MEN gastrinomas: a ten-year experience. 196 82

To our knowledge this is the first reported case of concurrent Merkel cell (trabecular carcinoma) tumor and peripheral pulmonary carcinoid tumor. Both tumors are considered to neuroendocrine in nature. The significance of concurrent neuroendocrine tumors is described with respect to multiple endocrine neoplasia syndrome variants and possible pathophysiology.
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PMID:Concurrent spindle cell peripheral pulmonary carcinoid tumor and Merkel cell tumor of the skin. 196 30

The development of assay techniques for the analysis of tumor markers in tissue extracts and in the peripheral circulation has had a major impact on the diagnosis and management of patients with endocrine neoplasms. In addition to eutopic and ectopic hormones, a variety of other tumor-derived products, including endocrine secretory proteins, enzymes, and oncodevelopmental antigens, can be assayed. The development of stimulatory tests to evaluate secretory reserve has been of particular value for the early detection of endocrine tumors and preneoplastic lesions in the multiple endocrine neoplasia syndromes. In addition, analysis of tumor markers has been of considerable importance for estimating total tumor burden and assessing responses to various therapeutic modalities. Recent advances in molecular biologic and cytogenetic technologies have the potential for prenatal detection of some forms of the inherited multiple endocrine neoplasia syndromes.
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PMID:Tumor markers in endocrine malignancies. 197 May 20

Multiple endocrine neoplasia type IIA (MEN IIA) syndrome is an autosomal-dominant endocrine disorder that consists of medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia. The susceptibility gene to this disorder has been mapped to chromosome 10. However, molecular studies of tumor cells from patients with familial and sporadic MTC and/or pheochromocytoma have shown a high frequency (50%) of abnormalities on chromosome 1p. In the present study, we examined MTC or pheochromocytoma tumor specimens from eight patients (familial and nonfamilial cases) to investigate gene losses on chromosomes 1 and 10 as potential mechanisms for the tumors' development. The patients studies had homozygous genotypes in their leukocyte DNAs for the chromosome 10 marker used in this study, and the patients were, therefore, uninformative. However, the patients were informative for the chromosome 1 markers and five of the patients' tumor-cell DNAs (63%) had allelic deletions at one or multiple loci on chromosome 1p, and one tumor DNA had evidence of possible gene rearrangement; in all six cases, the abnormalities involved the distal third of chromosome 1p. Furthermore, we determined that the common break point for the 1p deletions was at 1p32. These results suggest that a tumor suppressor gene in this defined region is involved in the development/progression of MTC and pheochromocytoma by being either lost or inactivated.
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PMID:Deletion mapping on the distal third region of chromosome 1p in multiple endocrine neoplasia type IIA. 197 9

The features of two patients with multiple endocrine neoplasia type IIb are described. Patient 1, a 9-year-old boy with marfanoid features, presented with chronic constipation and failure to thrive since infancy. Patient 2, a 12-year-old boy with marfanoid features, presented with a five-year history of persistent cervical lymphadenopathy. In patient 1, the myenteric and submucosal nerve plexuses at all levels of the small and large intestines were comprised of diffusely disorganized, hyperplastic, mature ganglion cells and nonmyelinated nerve fibers. Nerve plexus dissection with morphometric analysis showed marked thickening of the myenteric plexus with a quantitative increase in neural tissue. Patient 2 had a submucosal neuroma of the tongue. Both patients had occult medullary thyroid carcinoma, and patient 2 had cervical lymph node metastases. Both neoplasms showed positive staining for cytokeratin, carcinoembryonic antigen, calcitonin, bombesin, chromogranin, serotonin, and Leu 7. Electron microscopy showed membrane-bound, intermediate-sized, dense-core neurosecretory granules in tumor cells. In patient 2, calcitonin-positive amyloid was present with localization of calcitonin by immunoelectron microscopy to cytoplasmic secretory granules and to extracellular amyloid fibrils. These cases illustrate the potential for missed or delayed diagnosis in multiple endocrine neoplasia syndromes.
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PMID:Pathological features of multiple endocrine neoplasia type IIb in childhood. 197 36

A 58-year-old male patient with rectal carcinoid tumor is presented. The tumor extensively involved the lymph nodes and liver, and multiple tumors were also recognized in the pancreas and thyroid. Grossly, it was uncertain whether the latter were metastases from the rectal carcinoid or all were coincident primary tumors involving multiple endocrine organs, so-called multiple endocrine neoplasia (MEN) syndrome. Histologic, histochemical and electron microscopic examinations of the tumors in both the pancreas and thyroid showed similar features to those of the rectal carcinoid. The neoplastic cells in all involved organs commonly expressed positive immunoreactivity for somatostatin, but negativity for carcinoembryonic antigen, calcitonin, calcitonin gene-related peptide, thyroglobulin, insulin, glucagon and pancreatic polypeptide. These immunohistochemical results confirmed that the tumors observed in multiple endocrine organs were indeed metastatic from the rectal carcinoid, rather than being a new combination of MEN syndrome. Some neuroendocrine tumors may develop widespread metastasis, sometimes creating problems with differentiation from multiple primary endocrine tumors. Immunohistochemistry may be of great help in setting this issue.
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PMID:Rectal carcinoid tumor metastasizing to the thyroid and pancreas. An autopsy case exploiting immunohistochemistry for differentiation from tumors involving multiple endocrine organs. 197 68

Molecular genetic analysis was performed with 20 oncogene probes and 32 polymorphic DNA probes on tumor DNA samples from seven pheochromocytomas; namely, one multiple endocrine neoplasia type 2B, and two familial and four sporadic pheochromocytomas. No amplification or rearrangement of the oncogenes was detected in any of the tumors. However, loss of heterozygosity on chromosome 1p, 11p or 11q was detected in these cases. In addition, a locus related to ETS1 was deleted in two of the sporadic tumors. These results suggest that pheochromocytomas may be genetically heterogeneous, and that inactivation of unknown genes on chromosome 1p, 11p or 11q may contribute to their development.
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PMID:Loss of heterozygosity on chromosomes 1 and 11 in sporadic pheochromocytomas. 197 19

Multiple endocrine neoplasia type 1 is an autosomal dominant condition characterized by the development of parathyroid hyperplasia, pituitary adenomas, and pancreatic islet cell tumors. Recently the gene for multiple endocrine neoplasia type 1 was mapped to the long arm of chromosome 11 between the loci PGA and INT2. We tested the hypothesis that tumor development is the result of a somatic deletion that unmasks a constitutional mutation. By investigating DNA isolated from tumors and somatic tissues in 12 patients from 4 different families with multiple endocrine neoplasia type 1, we found loss of heterozygous markers mapped to 11q13 in 9 (82%) of 11 informative tumors. In contrast, we were unable to identify allelic loss from other chromosomes using a variety of informative probes. This high incidence of chromosomal deletion of 11q13 suggests that this region is important in the oncogenesis of this disorder.
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PMID:Loss of heterozygosity of markers on chromosome 11 in tumors from patients with multiple endocrine neoplasia syndrome type 1. 197 36

Medullary thyroid carcinoma (MTC) develops in all patients with multiple endocrine neoplasia type IIb (MEN IIb), a rare syndrome that either occurs sporadically or is inherited in an autosomal dominant pattern. The MTC in patients with MEN IIb has been reported to be biologically aggressive with onset at a young age and rapid progression as evidenced by widespread metastases and death, frequently in the teenage years. Seven children, aged 2 to 11 years (mean, 7 years), from three kindreds with MEN IIb were evaluated for evidence of tumor recurrence 3 to 10 years following thyroidectomy. In one child, age 11, a thyroid mass was palpable preoperatively. However, in the remaining six children (aged 2 to 10 years), the diagnosis of MTC was established by an increased concentration of plasma calcitonin (CT), either basally or following pentagastrin (Pg) stimulation. All patients underwent total thyroidectomy with removal of central lymph nodes from the neck. At the time of surgery, six children were found to have bilateral macroscopic MTC, five without and one with cervical metastases. One child (age 2 years) had C-cell hyperplasia, a premalignant precursor of MTC. Currently, five of the seven children are without evidence of recurrent disease clinically and have normal plasma CT levels (less than 0.3 ng/mL) following calcium (Ca) and Pg stimulation 3, 3, 10, 10, and 10 years after thyroidectomy. Two of the seven children have biochemical evidence of residual MTC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of children with multiple endocrine neoplasia type IIb following thyroidectomy. 197 72


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