Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ret/PTC oncogene is unique to papillary thyroid cancer. Three forms of this oncogene, formed by translocation of three different genes to the tyrosine kinase domain of the ret protooncogene, result in constitutive kinase activation. Correlation with clinical outcome is controversial; ret/PTC-1 has been suggested to predict aggressive behavior. There is no morphological description of ret/PTC-positive tumors. We analyzed 60 thyroid carcinomas for ret/PTC expression to determine correlation with clinical history, disease stage, or tumor morphology. Ribonucleic acid extracted from frozen tissue was reverse transcribed; PCR was performed to amplify ret/PTC-1, 2, and -3. The TPC-1 cell line was the positive control for ret/PTC-1. All tumors were characterized morphologically. Clinical data were collected. The 57 papillary and 3 follicular carcinomas were resected from 44 female patients and 15 males. The average age at diagnosis was 46.2 yr (range. 24-83 yr). Three patients had a history of neck irradiation. At diagnosis, 11 patients had extrathyroidal tumor extension, 20 had lymph node metastases, and 1 had lung metastasis. Thirteen patients had tall cell papillary carcinomas; 3 tumors had focal insular or anaplastic dedifferentiation. The average follow-up was 13.4 months, during which 4 patients had recurrent disease. No deaths occurred. One papillary carcinoma (1.7%) was positive for ret/PTC-1, none was positive for ret/PTC-2, and 2(3.4%) were positive for ret/PTC-3. Although all 3 patients who had tumors containing ret/PTC rearrangements were under the age of 45 yr (range, 26-44 yr) and had small tumors (< 1.2 cm), 2 of these 3 patients presented with lymph node metastases, and the third had lymphatic invasion. ret/PTC oncogene expression did not correlate with radiation history. In summary, ret/PTC oncogene rearrangements were found in 3 of 60 (5%) thyroid carcinomas and were not present in tumors with aggressive morphological features. However, we found ret/PTC rearrangements in young patients (< 45 yr of age) with small thyroid carcinomas showing a predisposition for lymphatic involvement, suggesting a possible role in the development of this subgroup of tumors.
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PMID:ret/PTC-1, -2, and -3 oncogene rearrangements in human thyroid carcinomas: implications for metastatic potential? 914 69

Lymph node metastases at presentation are common in PTC and MTC (about one third of patients at presentation), but are rare in other types of thyroid malignancy, though HCC frequently recurs in lymph nodes. Nodal metastases can be detected by a variety of means, but high resolution ultrasonography may be the method of choice. Unlike other epithelial malignancies, in thyroid cancer neither prognostic significance nor optimal treatment of nodal metastasis are known with certainty. For PTC lymph node metastases at presentation do not seem to adversely affect survival, but do increase the risk of locoregional tumor recurrence. By contrast, in FTC nodal metastases at presentation may adversely affect cause-specific mortality, but because of their rarity definite conclusions are impossible. Except for the oxyphilic variant of FTC (HCC) nodal recurrence in FTC is rare. The most firm evidence of prognostic relevance for nodal metastases in thyroid malignancies exists in medullary thyroid cancer, where most studies suggest that survival and recurrence are both adversely affected by node-positive status at presentation. Primary treatment of nodal metastases is removal of macroscopically affected nodes at initial surgery, optionally supplemented with adjuvant radioiodine treatment in an attempt to reduce recurrence risk. The value, however, of postoperative radioiodine in preventing either nodal recurrence or cancer death in patients with papillary and follicular thyroid cancer remains controversial. Extensive lymph node dissection at presentation offers no advantage (and may cause increased morbidity) in papillary carcinoma, but may be useful in medullary thyroid carcinoma, where nodal metastases seem to increase the risk of cause-specific mortality. In all tumor types postoperative nodal recurrences should primarily be treated surgically.
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PMID:Thyroid cancer nodal metastases: biologic significance and therapeutic considerations. 878 93

The concept of congenital biliary dilatation (CBD) was established by Alonso-Lej whose classification has been widely accepted and become a standard. Todani, Komi and several investigators then added additional subclassifications and/or made a proposal of new classification. The trias, abdominal pain, abdominal mass and jaundice, had been characteristically found in these cases, but recently asymptomatic cases are often found. Many reports have shown that the cases with cystic dilation of the biliary duct frequently associated with biliary carcinoma and pancreaticobiliary maljunction (PBM), an anomalous union of pancreatic duct with biliary tree since the Rabbit's first report. Whereas extracorporeal ultrasound and CT scan are minimally invasive diagnostic procedures for these cases, a direct cholangiography, ERCP and PTC are the diagnostic procedures that make a definite diagnosis for the appropriate treatment. Recently, endoscopic ultrasound (EUS), helical CT and magnetic resonance cholangiopan-creatography (MRCP) have drawn an attention since these methods are less invasive than those ever being used. In particular, MRCP will be suitable for the screening of preoperative examination. Whereas cystoduodenostomy used to be performed in the past for these cases, the resection of dilatted bule duct along with the diversion of bile from pancreatic juice should be performed to prevent biliary carcinoma. Cholecystectomy along with the resection of bile duct and the biliary diversion from pancreatic juice should also be performed for cases of PBM without CBD because mutagenicity of bile mixed with pancreatic juice and K-ras point mutation in noncancerous bile duct epithelium in cases of PBM without CBD were demonstrated.
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PMID:[Symptoms, diagnosis and treatment of pancreaticobiliary maljunction associated with congenital cystic dilatation of bile duct]. 890 5

This article discusses several unusual forms of primary thyroid neoplasms. The TCV of PTC and insular thyroid carcinoma appears to have a more aggressive clinical behavior than DTC in most patient groups and may respond to thyroid hormone suppression and radioiodine. Anaplastic thyroid carcinoma, which may develop from differentiated thyroid tumors, has a poor prognosis which may be altered by surgery and radiation therapy but not typically by radioiodine and thyroid hormone suppression. Primary squamous cell carcinoma of the thyroid is an unusual entity that may be associated with a clinical syndrome that includes leukocytosis, fever, and hypercalcemia. Primary thyroid lymphoma is frequently associated with Hashimoto's thyroiditis and should be considered especially in older patients with rapidly enlarging thyroid masses. Although there are no studies assessing this issue, it seems reasonable that patients who have undergone thyroidectomy for neoplasms of thyroid cells that are poorly differentiated and do not concentrate radioiodine (e.g., squamous cell, anaplastic) should receive sufficient thyroid hormone suppression, if tolerated, to reduce TSH (third-generation assay) to approximately 0.1 to 0.3 mu U/mL, because TSH may be a growth factor. If, however, the tumor concentrates or responds to radioiodine, suggesting more differentiated cells (e.g., TCV, insular carcinoma), the target TSH level (third-generation assay) should range from 0.01 to 0.1 mu U/mL, as tolerated. Patients with primary thyroid neoplasms arising from cells other than thyrocytes (e.g., lymphoma) can be maintained at a TSH level of 0.5 to 1.5 mu U/mL. Our conclusions and analyses are often based upon small, retrospective, poorly controlled reports, and further studies are required to allow a better understanding of the evaluation and treatment of these neoplasms.
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PMID:Unusual types of thyroid neoplasms. 890 80

The aim of this study was to determine the apoptotic cell death in 92 thyroid carcinomas of different histotypes (42 papillary, PTC; 12 poorly differentiated, PDC: 21 undifferentiated, UC; and 17 medullary, MC) by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labelling (TUNEL). Apoptotic index (Al, evaluated as a percentage of TUNEL-positive cells of neoplastic cells) was calculated in each tumour. The AI was very low in all subtypes of thyroid carcinoma, ranging from a median value of 0.2 in PTC to 1.4 in UC. The proliferative activity was determined by immunohistochemistry using monoclonal antibody, MIB-1. The percentage of proliferating cells was significantly different among the histotypes, increasing with tumour aggressiveness (from the mean value of 3.1 for PTC to 5.6 for PDC and 51.8 for UC). In addition, the ratio between proliferative activity and apoptosis was significantly higher in UC than in the other histotypes. The expression of bcl-2 and p53 protein (important in the modulation of cell death) was correlated (bcl-2, inverse correlation, r2 = 0.1, P = 0.04; p53, direct correlation, r2 = 0.11, P = 0.02) with apoptotic index in PTC.
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PMID:Apoptosis and proliferation in thyroid carcinoma: correlation with bcl-2 and p53 protein expression. 905 6

Thyroid carcinomas, even when well differentiated, usually appear as hypofunctioning at scintigraphy. We report a case of an aggressive insular thyroid carcinoma presenting as an autonomously functioning thyroid nodule and causing severe thyrotoxicosis. The tumor was metastatic to a cervical lymph node and both lungs. An activating mutation of the TSH receptor gene in both the primary tumor and the lymph node metastasis was found, due to a base substitution at codon 633 (normal guanine at position 1896 replaced by cytosine CAC for GAC causing aspartic acid substitution by histidine). Other known oncogenes (gsp, ras, PTC/ret, trk, met, and p53) were not involved. This is the first description of an activating TSH receptor mutation in a thyroid hyperfunctioning carcinoma in which an aggressive malignant phenotype coexisted with activation of the cAMP cascade and differentiated thyroid functions.
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PMID:Detection of an activating mutation of the thyrotropin receptor in a case of an autonomously hyperfunctioning thyroid insular carcinoma. 936 May 62

The sequence-tagged site (STS) D10S170, also referred to as H4, is a gene of unknown function. Its 5' end was found fused to the catalytic domain of the RET protooncogene to generate RET/PTC 1, the most common form of PTC oncogenes in human papillary thyroid carcinoma. This gene has previously been assigned to a very large genomic region, 10q11.22-->q22.1. Here, we describe the application of a novel hybridization scheme to the physical and genetic mapping of D10S170. First, we selected a homologous large-insert DNA clone from a human P1 library by filter hybridization and confirmed its authenticity by Southern blot analysis. Triple-color fluorescence in situ hybridization (FISH) experiments mapped this clone to l0q21.2-->q21.3. "Binning" experiments were performed using a quadruple-color FISH approach aimed toward placing the gene in a genetic interval defined by differentially labeled P1 DNA probes containing known polymorphic markers. We found that multicolor FISH greatly expedites chromosomal mapping. Finally, we applied our FISH approach to determine the extent of deletion involving this locus (D10S170) in a papillary thyroid cancer cell line, TPC-1.
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PMID:A novel multicolor hybridization scheme applied to localization of a transcribed sequence (D10S170/H4) and deletion mapping in the thyroid cancer cell line TPC-1. 906 36

In this study, we compare the morphological and genetic characteristics of 38 post-Chernobyl thyroid papillary carcinomas from Belarussian children 5-18 years old with those of 23 sporadic papillary carcinomas from the same age children without history of radiation exposure from Los Angeles and Cincinnati. Among radiation-induced tumors, solid variant of papillary carcinoma was found in 37%, follicular in 29%, typical papillary in 18%, and mixed and diffuse sclerosing variants in 8% each. In the sporadic group, a typical papillary pattern was prevalent in 70%, follicular in 17%, diffuse sclerosing variant in 9%, and solid in 4%. In both groups, the prevalence of ret rearrangements was high, but the frequency of specific types of rearrangement was significantly different. Among radiation-induced tumors, ret/PTC3 was found in 58%, ret/PTC1 in 16%, and ret/PTC2 in 3%, whereas among sporadic tumors, ret/PTC1 was found in 47% (P < 0.05), and ret/PTC3 was found in 18% (P = 0.01). The morphological variants of papillary carcinoma showed different prevalence of the specific types of ret rearrangement. Seventy-nine % of solid variant tumors had ret/PTC3, whereas only 7% had ret/PTC1 (P = 0.0007). Among typical papillary tumors, ret/PTC1 was found in 38%, ret/PTC3 in 19%, and ret/PTC2 in 5%. Thus, ret rearrangements are highly prevalent in pediatric papillary carcinomas from children exposed to radiation and in those occurring sporadically. However, the types of ret/PTC vary between these two populations, with ret/PTC3 present more commonly in post-Chernobyl tumors. Furthermore, solid variants have a high prevalence of ret/PTC3, whereas typical papillary carcinomas do not, suggesting that the different types of ret rearrangement confer neoplastic thyroid cells with distinct phenotypic properties.
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PMID:Distinct pattern of ret oncogene rearrangements in morphological variants of radiation-induced and sporadic thyroid papillary carcinomas in children. 913 9

Extracellular nucleotides like ATP that activate the Ca2+ -phosphatidylinositol (PI) signalling pathway have been suggested to participate in the regulation of normal human thyroid function. We examined, whether P2y-purinergic receptors are expressed on human thyroid cancer cells and whether post-receptor Ca2+ signalling is altered by malignant transformation. Extracellular ATP caused a biphasic increase in cytosolic free Ca2+ ([Ca2+]i) in normal human thyrocytes and in human follicular (FTC) and papillary (PTC) thyroid carcinoma cells. In FTC and PTC cell lines the dose-response curves for ATP-induced changes in [Ca2+]i were shifted to the right when compared with normal thyrocytes, whereas in undifferentiated thyroid carcinoma (UTC) cells even high concentrations of ATP (500 microM) failed to stimulate a rise in [Ca2+]i. By contrast, ATP stimulated inositol 1,4,5-trisphosphate (IP3) formation and capacitative Ca2+ entry was operational as judged by thapsigargin in normal thyrocytes and all thyroid cancer cells. Thus, P2y-purinergic receptors are expressed on thyroid tumor cells independent of degree of differentiation. In UTC cells, however, impairment in the Ca2+ -phosphatidylinositol (PI) signalling cascade occurs distal to the formation of IP3 and proximal to the activation of capacitative Ca2+ entry. Disturbed ATP-induced Ca2+ -signalling and alterations in the Ca2+ -PI signalling cascade may contribute to decreased expression or loss of specific thyroid functions in thyroid cancer cells.
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PMID:Impairment of ATP-induced Ca2+ -signalling in human thyroid cancer cells. 935 70

We have examined the coexpression of hepatocyte growth factor (HGF) and its receptor (HGF-R or c-met) in an archival series of 63 paraffin-embedded thyroid specimens plus one lymph node metastasis. By immunocytochemistry, we found undetectable expression of both the ligand and the receptor in 10 normal thyroids and 9 nonpapillary malignant nodules [5 follicular carcinomas, 1 poorly differentiated (insular) carcinoma, 3 undifferentiated (anaplastic) carcinomas]. Of 10 non-neoplastic nodules (colloid nodules) and 17 benign neoplastic nodules, 3 of 10 colloid nodules, 2 of 10 follicular adenomas, and 2 of 7 oncocytic adenomas showed a weak but distinct staining (1+ score in a scale from 0 to 4+) of both HGF and c-met in a modest proportion of cells (1% to 3%). In these 7 cases, expression of HGF was always stromal and expression of c-met limited to the membrane of the follicular cells. Of 3 malignant nodules derived from aberrant growth of the parafollicular C cells (medullary thyroid cancer or MTC), 2 were positive (6% of cells). In these 2 cases, the expression of HGF (3+) was not stromal, but in both the membrane and cytoplasm of the parafollicular cells, while that of c-met (3+) was restricted to the membrane. In contrast to all of the above, of 14 papillary carcinomas (PTC) encompassing 5 histological variants (conventional; follicular; oncocytic; with foci of solid growth; diffuse sclerosing) plus 1 neck lymph node metastasis of 1 conventional PTC, 12 (86%) expressed HGF, and 13 (93%) expressed c-met. With the exception of 2 negative cases, HGF was detected in 15% to 46% of the cells. The highest percentage (46%) pertained to conventional PTC cases with abundant peritumoral lymphocyte infiltration, indicating that some lymphokine(s) may recruit PTC cells for HGF expression in a paracrine fashion. With the exception of one negative case, c-met was found in 43% to 80% of the cells, both at levels from intense (3+) to very intense (4+). The immunostaining for HGF was stromal in 25%, membranous in 8%, cytoplasmic in 8%, and both membranous and cytoplasmic in 59% of the PTC-positive cases. The immunostaining for c-met was membranous in 43% and both membranous and cytoplasmic in 57% of the PTC-positive cases. In the lymph node metastasis and in the diffuse sclerosing variant of PTC (the most aggressive variant), the coexpression of HGF/c-met was lost, in that only c-met was expressed on membranes in both cases. We conclude that the HGF/c-met system is activated (by overexpression of both components) in the vast majority of PTC. In most PTC the interaction of HGF and its receptor (c-met) is autocrine, not paracrine.
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PMID:Expression of the hepatocyte growth factor and c-met in normal thyroid, non-neoplastic, and neoplastic nodules. 951 Jan 20


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