Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The RET proto-oncogene encodes a receptor tyrosine kinase for transforming growth factor-beta-related neurotrophic factors, which include GDNF and neurturin. The expression of RET proto-oncogene was detected in several tissues, such as spleen, thymus, lymph nodes, salivary gland, and spinal cord, and in several neural crest-derived cell lines. RET expression in the thyroid gland was reported to be restricted to neural crest-derived C cells. The presence of RET mRNA or protein has not yet been reported in thyroid follicular cells. We previously demonstrated the expression of oncogenic rearranged versions of RET in papillary thyroid carcinomas: tumors derived from thyroid follicular cells. To assess the expression of the normal RET proto-oncogene in follicular cells, we analyzed its expression in a panel of neoplasias originating from thyroid follicular epithelial cells: papillary carcinomas and both follicular adenomas and carcinomas. We also demonstrated the presence of RET normal transcripts in two follicular thyroid carcinoma lymph node metastases. Moreover, we found the presence of the RET/ELE1 transcript, the reciprocal complementary form of the oncogenic fusion transcript ELE1/RET, in a papillary thyroid carcinoma specimen expressing the RET/PTC3 oncogene, thus demonstrating that the RET promoter is active in those cells after rearrangement. Finally, we show that in a papillary carcinoma-derived cell line expressing the proto-RET receptor and the related GFRalpha2 co-receptor, GDNF treatment induced RET tyrosine phosphorylation and subsequent signal transduction pathway, indicating that RET could be active in thyroid follicular cells.
 ...
PMID:RET receptor expression in thyroid follicular epithelial cell-derived tumors. 1085 Apr 26

We have determined the frequency of 918 RET proto-oncogene mutations (ATG-->ACG) in primary MTC tumors and metastases and correlated the presence or absence of this mutation with the clinical outcome of patients suffering from sporadic medullary thyroid carcinoma (MTC). A total of 197 samples, consisting of both primary tumors and lymph node metastases from 34 patients with sporadic MTC, were collected for PCR analysis of the RET 918 mutation. In 75 of the samples (38%), codon 918 (ATG-->ACG) mutations could be detected. The mutations showed a heterogeneous distribution: 21/34 patients (62%) had mutations in at least 1 tumor sample, and in 13 patients (38%) the mutation was present in all examined samples. Patients were considered 918mt when at least 1 tumor sample showed the RET 918 mutation. These 918mt and 918 wild-type (918wt) patients did not differ significantly concerning sex, age at diagnosis, TNM stage at diagnosis, number of examined tumor samples or follow-up time. However, 918mt patients showed more aggressive development of distant metastases during follow-up (p = 0.032, Fisher's exact test) with decreased metastases-free survival (p < 0.005, log-rank test). Furthermore, 918mt patients had a significantly lower survival rate than 918wt patients (p = 0.048, log-rank test). These data show that the RET codon 918 mutation has a prognostic impact on patients with sporadic MTC which may influence follow-up treatment.
 ...
PMID:Prognostic value of codon 918 (ATG-->ACG) RET proto-oncogene mutations in sporadic medullary thyroid carcinoma. 1124 13

Medullary carcinoma of the thyroid (MTC) is a rare tumour derived from thyroid C cells with serum calcitonin as a specific and sensitive marker. MTC is inherited in 25% of cases, with an autosomal dominant transmission, age-related penetrance and variable expressivity. MTC is an obligatory component of multiple endocrine neoplasia type 2 (MEN2), which comprises three well defined syndromes: MEN2A, which may be associated with pheochromocytoma and/or hyperparathyroidism; the much rarer MEN2B, which occurs early and is accompanied by developmental abnormalities; while in contrast, familial MTC (FMTC) is not associated with any endocrinopathy. The RET proto-oncogene is the causative gene of the MEN2 syndromes and mutations in this gene are found in >90% of inherited cases, allowing easier and more reliable family screening than pentagastrin stimulation tests. Nevertheless, the correlation between the genotype and the different clinical phenotypes is not perfect. The prognosis of MTC depends on its staging at presentation, and the early appearance of cervical lymph node metastases emphasizes the need for extensive surgery, although many patients still do not normalize calcitonin levels post-operatively, and they remain a challenge for the further management.
 ...
PMID:Diagnosis and treatment of medullary thyroid cancer. 1128 39

We report herein the case of a 77-year-old woman found to have mixed medullary-papillary carcinoma in the right thyroid with lymph node metastases 30 years after a left thyroidectomy. The preoperative values of serum calcitonin and carcinoembryonic antigen (CEA) were high, and fine-needle aspiration biopsy revealed class V, which led us to suspect papillary carcinoma. A right thyroidectomy with dissection of the right neck lymph nodes was performed. Histopathological examination of the tumor specimens revealed gradual borders between medullary carcinoma and papillary carcinoma with positive immunohistochemical staining to calcitonin, chromogranin A, CEA, and thyroglobulin. The serum levels of calcitonin and CEA decreased to normal after the operation. The point mutation of the RET proto-oncogene was found to be negative by a DNA analysis of the peripheral leukocytes. This cancer seemed not to be associated with multiple endocrine neoplasia type 2 syndrome. The presence of both medullary and papillary components in the thyroid with lymph node metastases is rare and may suggest that the tumor had arisen from a common stem cell.
 ...
PMID:Mixed medullary-papillary carcinoma of the thyroid with lymph node metastases: report of a case. 1132 40

Multiple endocrine neoplasia (MEN) type 2B is a heritable endocrine disorder characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, multiple mucosal neuromas, and a marfanoid habitus. Intestinal ganglioneuromatosis, corneal nerve thickening and skeletal abnormalities are also often present. The disease is inherited in an autosomal dominant fashion and is caused by a single mutation in the RET proto-oncogene, with a methionine to threonine substitution at codon 918. The MTC in MEN 2B presents at an earlier age and tends to be more aggressive than the MTC in MEN 2A. It is multicentric and bilateral and occurs as young as age 3, with early lymph node metastases. Pheochromocytoma is also often bilateral but is rarely malignant. If pheochromocytoma is detected, adrenalectomy should precede thyroidectomy to avoid intraoperative catecholamine crisis. Patients at risk for MEN 2B should undergo genetic screening in infancy. Total thyroidectomy should be performed on all patients positive for RET mutations even prior to the onset of clinical symptoms.
 ...
PMID:Multiple endocrine neoplasia type 2B--genetic basis and clinical expression. 1135 39

Patients with clinically evident medullary thyroid cancer should have a total extracapsular thyroidectomy with bilateral central neck dissection and an ipsilateral prophylactic or therapeutic modified (functional) radical neck dissection when the primary tumor is greater than 1 cm and when the central neck nodes are positive. A prophylactic contralateral neck dissection should be done when the primary tumor is bilateral and when there is extensive lymphadenopathy on the side of the primary tumor. Patients who have gross, unresectable residual medullary thyroid cancer should receive postoperative external radiotherapy. Patients who are carriers of germ-line RET proto-oncogene point mutations or have an elevated (basal or stimulated) calcitonin levels on screening should have a prophylactic total thyroidectomy before age 6 years. In patients with an elevated basal or stimulated plasma calcitonin level and an intrathyroidal nodule on ultrasound, a total thyroidectomy and central neck lymph node dissection should be done. Patients with persistent or recurrent medullary thyroid cancer should have a complete thyroidectomy (if not done initially) and bilateral central and modified radical neck dissection, including upper mediastinal lymphadenectomy. Patients who are symptomatic from distant medullary thyroid cancer metastases (diarrhea, flushing, weight loss, or bone pain) should be treated with somatostatin analogs. Bone metastases should be resected if possible, and symptomatic lesions that are unresectable should be treated with external radiotherapy. Cytoreductive procedures such as radiofrequency ablation or cryoablation for liver metastases should be considered in symptomatic patients to reduce tumor burden. Localized pulmonary metastases should be resected. Chemotherapy or radioactive immunotherapy (iodine 131 labeled carcinoembryonic antigen monoclonal antibody) protocols should be considered in patients with nonoperative widely metastatic progressing medullary thyroid cancer.
 ...
PMID:Medullary thyroid cancer. 1205 61

Medullary thyroid carcinoma (MTC) is a malignancy of the parafollicular C cells of the thyroid gland. It occurs sporadically or as part of the multiple endocrine neoplasia type 2 (MEN 2) syndromes. Patients who have inherited a mutation in the RET proto-oncogene should have thyroidectomy early in life to prevent formation and spread of this cancer. Most patients with sporadic disease present with a palpable neck mass. The diagnosis is made by fine needle aspiration biopsy and by measuring calcitonin levels in the blood. Primary treatment consists of surgical resection including a total thyroidectomy, central neck nodal dissection and functional lateral neck nodal dissections. Most patients with a palpable primary tumour have nodal disease present at the time of operation, and nodal involvement is often bilateral. Adequate resection of the primary tumour and cervical lymph nodes is important to optimize outcome and minimize the risk of recurrent disease. Proper handling of the parathyroid glands prevents hypoparathyroidism. Following primary surgical resection, more than half of the patients will have recurrent disease with persistent elevation of calcitonin levels. Currently, there is no adequate systemic therapy for treating recurrent disease. Surgical reoperation or conservative observation are the best available options. Diagnostic laparoscopy for liver evaluation is the most sensitive diagnostic test to detect the presence of distant metastases.
 ...
PMID:Surgical treatment of medullary thyroid carcinoma. 1275 57

We report the case of a 72 yr-old woman who underwent total thyroidectomy and resection of neck lymph nodes because of a firm nodule in the right lobe, which was consistent with medullary thyroid carcinoma (MTC) on cytological examination. Histology showed multifocal bilateral MTC; a 2 mm papillary thyroid carcinoma (PTC) was also detected in the right lobe, next to a focus of MTC; five cervical lymph nodes contained MTC. In one right perithyroidal lymph node, concurrent metastases of MTC and PTC were demonstrated. DNA analysis showed a point mutation in exon 14 at codon 804 of the RET proto-oncogene locus, as frequently found in cases of familial MTC (FMTC). To our knowledge, this case represents the first documented case of concurrent lymph node metastases of MTC and PTC in a patient with RET proto-oncogene germline mutation. We report this unique case, discuss related thyroid malignancies, and suggest possible underlying pathogenetic mechanisms.
 ...
PMID:Concurrent lymph node metastases of medullary and papillary thyroid carcinoma in a case with RET oncogene germline mutation. 1458 73

Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy, which is familial in 25-29% of cases. Familial MTC is due to germ-line mutations in the RET proto-oncogene. It can occur either alone or as the thyroid manifestation of MEN 2 syndromes; the disease is inherited in an autosomal dominant fashion with age-related penetrance. The treatment of choice is surgery. Early diagnosis and an adeguate initial operation provide the best chance of cure. Hence, the diagnosis should be made preoperatively. Genetic testing can identify almost all affected individuals with hereditary disease and permits prophylactic/early thyroidectomy in gene carriers. Total thyroidectomy and lymphadenectomy of the cervicocentral compartment is mandatory in all patients. In addition, bilateral dissection of the cervicolateral compartment should be done in all cases with more than microscopic disease. Plasma calcitonin is an excellent marker for postoperative follow-up. Treatment of persistent/recurrent disease is primarily surgical. Hence, a reoperative cervical lymphadenectomy should be considered in patients with persistently elevated calcitonin levels and no signs of distant metastases. Chemotherapy and external radiotherapy have little impact on the course of avanced disease; more promising is metabolic radiotherapy with Y90-DOTATOC in patients with somatostatin receptor-positive tumours.
 ...
PMID:[Treatment of familial medullary thyroid carcinoma]. 1466 8

Medullary thyroid carcinoma (MTC) arises from parafollicular or C cells that produce calcitonin (CT), and accounts for 5-10% of all thyroid cancers. MTC is hereditary in about 25% of cases. The discovery of a MTC in a patient has several implications: disease extent should be evaluated, phaeochromocytoma and hyperparathyroidism should be screened for and whether the MTC is sporadic or hereditary should be determined by a direct analysis of the RET proto-oncogene. In this review, pathological characteristics, tumour markers and genetic abnormalities in MTC are discussed. The diagnostic and therapeutic modalities applied to patients with clinical MTC and those identified with preclinical disease through familial screening are also described. Progresses concerning genetics, initial treatment, follow-up, screening and treatment of pheochromocytoma have permitted an improvement in the long-term outcome. However, there is no effective treatment for distant metastases, and new therapeutic modalities are urgently needed.
 ...
PMID:Medullary thyroid carcinoma. 1535 45


<< Previous 1 2 3 4 Next >>