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

Papillary (PTC) and follicular thyroid carcinoma (FTC) are known as differentiated thyroid carcinoma (DTC). Nevertheless, according to the UICC/AJCC (TNM) classification PTC and FTC are frequently analyzed as one cancer. The aim of this study is to show differences in outcome and specific prognostic factors in an iodine-replete endemic goiter region. Six hundred and three patients with DTC treated within a 35-year-period were retrospectively analyzed with respect to carcinoma-specific survival. Prognostic factors were tested for their significance using univariate and multivariate analysis. The histological type (PTC versus FTC) was found to be a highly significant factor - carcinoma-specific survival both in univariate (P<0.001) and multivariate analyses (P=0.003) was significantly different. Univariate analysis revealed patients' age, extra-thyroid tumor spread, lymph node and distant metastases, increasing tumor size, and the tall cell variant to be significant prognostic factors for PTC patients. Age > or =45 years, positive lymph nodes and increasing tumor size were confirmed as independent prognostic factors. Univariate analysis of FTC patients revealed age at presentation, gender, extrathyroidal tumor spread, lymph node and distant metastases, increasing tumor size, multifocality, widely invasive tumor growth and oxyphilic variant to be factors bearing prognostic significance. The presence of distant metastases and increasing tumor size could be identified as independent prognostic factors for FTC patients. This study shows distinctive differences in prognostic factors of PTC and FTC: independent factors predicting poor prognosis are age > or =45 years, positive lymph nodes and increasing tumor size for PTC, and distant metastases and increasing tumor size for FTC. PTC and FTC patients should be analyzed and reported separately.
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PMID:Prognostic factors of papillary and follicular thyroid cancer: differences in an iodine-replete endemic goiter region. 1502 90

CD82 (KAI1) and CD63 (ME491) are highly glycosylated proteins which belong to the transmembrane 4 superfamily (TM4SF). CD82 has been implicated as a possible prostate cancer metastasis suppressor gene, whereas CD63 is involved in the progression of human melanoma cancer. Down-regulation of both CD82 and CD63 expression has been associated with the metastatic potential of several solid tumors. Currently, information is lacking on the role of CD82 and CD63 during thyroid carcinogenesis. The aim of this study was to determine whether the expression of CD82 and CD63 is a useful prognostic indicator in patients with thyroid carcinoma. The expression of CD82 and CD63 was analysed by reverse transcriptase-PCR (RT-PCR) and immunohistochemistry in benign goiter (n=12) and 75 primary thyroid carcinoma tissue specimens (PTC: 33, FTC: 24, UTC: 18) out of which 36 were non-metastasized primary tumors and 39 were metastasized tumors (regional lymph node and/or distant metastases). All of the benign goiter tissues showed CD82 expression. By contrast, a significant decrease in CD82 mRNA and protein levels was detected in carcinoma tissues as compared to benign goiter tissues (p<0.001). A similar down-regulation was observed in metastasized tumor tissues when compared with non-metastasized tumors (all p<0.05). CD82 expression was correlated with pTNM status of differentiated and undifferentiated thyroid tumor and the pathologic stage of differentiated thyroid tumor. In contrast to CD82, CD63 mRNA and protein expression was unchanged in all thyroid carcinomas. Benign goiter tissues showed weak expression of CD63. There were no significant correlation between CD63 mRNA/protein expression and any clinical/pathological parameters. Our results support the hypothesis that down-regulation of CD82 expression may reflect an increased in vivo metastatic potential of thyroid cancer cells. CD82 may serve as a prognostic marker of metastasis in thyroid cancer. Constitutive expression of CD63 may indicate that this factor does not play a direct role in thyroid carcinogenesis.
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PMID:CD82, and CD63 in thyroid cancer. 1537 77

The incidence of epithelial derived thyroid cancer (papillary thyroid cancer and follicular thyroid cancer, known collectively as differentiated thyroid cancer) is rising. About 80% of patients with thyroid cancer have PTC and are best treated with thyroidectomy and functional lymph node dissection, followed by radioiodine ablation or therapy and performance of a posttreatment whole-body scan, followed by thyroid stimulating hormone (TSH) suppression. One year after radioiodine administration, the use of sensitive thyroglobulin (Tg) assays can separate the vast majority of patients with persistent disease from those who are free of disease and unlikely to have recurrent disease all without the need for repeat whole-body radioiodine imaging. Patients with detectable serum Tg during TSH suppression (Tg-on) or Tg that rises above 2 ng/mL after TSH stimulation (TSH-Tg) are highly likely to harbor residual tumor. TSH stimulation can be achieved using either thyroid hormone withdrawal or recombinant human TSH (rhTSH). Highly skilled screening neck ultrasonography can identify a few additional patients with subcentimeter residual neck lymph node metastases not detected by TSH-Tg. However, ultrasonography and chest computed tomography (CT) are most critical for tumor localization in those patients with Tg values that suggest residual disease or in those patients with persistent antithyroglobulin antibodies (TgAb) that falsely lower Tg measurement. TgAb quantitative titers typically resolve steadily over just a few years in patients free of disease after initial therapy. Another paradigm shift is the recognition that most patients who eventually achieve freedom from disease do so by surgery with fewer patients cured by repetitive radioiodine treatments, and even fewer cured with external beam radiation. Patients who appear to be free of disease require a lifetime of follow-up to optimize levothyroxine treatment, and they will undergo periodic stimulation testing because some will still manifest recurrent disease. Patients with persistent disease despite negative ultrasonography, chest CT, and whole-body radioiodine imaging may have a tumor identified by fluorodeoxyglucose positron emission tomography, optimally performed with combined TSH stimulation and image fusion with CT or magnetic resonance imaging. Patients with metastatic disease who are unresponsive to conventional treatment are encouraged to participate in increasingly available thyroid cancer-specific clinical trials using targeted experimental oral or intravenous chemotherapeutic agents to address this tumor that has historically proven resistant to conventional chemotherapeutic agents.
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PMID:Papillary thyroid cancer: medical management and follow-up. 1596 85

Papillary carcinoma is the most common type of thyroid malignancy. It has been recently shown that these tumors commonly have one of three genetic alterations: BRAF point mutations, RET/PTC rearrangements, or RAS point mutations. In this study, we analyze the relationship between these alterations and the microscopic features of papillary carcinomas, their clinical features, and prognostic characteristics. Ninety-seven papillary carcinomas were studied; in all cases, frozen tissue was available for nucleic acid extraction. Of 96 unselected cases, 42% were positive for BRAF, 18% for RET/PTC, and 15% for RAS mutations. Morphologic features were evaluated in detail in 61 cases and 6 characteristic nuclear features and 3 additional microscopic features were assessed quantitatively. At least 4 nuclear features were found in each tumor, with nuclear pseudoinclusions being the least frequent finding in all mutation groups. BRAF mutations were associated with older patient age, typical papillary appearance or the tall cell variant, a higher rate of extrathyroidal extension, and more advanced tumor stage at presentation. RET/PTC rearrangements presented at younger age and had predominantly typical papillary histology, frequent psammoma bodies, and a high rate of lymph node metastases. Tumors with RAS mutations were exclusively the follicular variant of papillary carcinoma and correlated with significantly less prominent nuclear features and low rate of lymph node metastases. These findings demonstrate that BRAF, RET/PTC, and RAS mutations are associated with distinct microscopic, clinical, and biologic features of thyroid papillary carcinomas.
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PMID:Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. 1643 96

Papillary thyroid carcinoma with nodular fasciitis-like stroma (PTC-NFS) is one of the extremely rare variants of papillary thyroid carcinoma. To date, the majority of reported cases have been published in the surgical pathology and cytopathology literature, addressing the diagnostic difficulties posed by the condition's extensive, reactive stromal proliferation. Because of the rarity of PTC-NFS among papillary thyroid carcinoma variants, it has been unexplored from a clinical viewpoint. A MEDLINE search on the clinical course, role of radioiodine, treatment outcome and long term follow up of this disease yielded no result.We report the clinicoradiologic and histopathologic profile, together with post-treatment long term follow up, in a 35-year-old woman harbouring this rare entity. To the best of our knowledge, this is the first report of a five-year follow up of this rare variant of PTC following total thyroidectomy and radioiodine treatment. Our follow-up findings reiterate the disease's favourable clinical course when managed in the same manner as a classical, differentiated papillary carcinoma of the thyroid, akin to that predicted by the pathologists, and emphasize the importance of differentiating PTC-NFS as a separate entity from the papillary carcinoma variants with aggressive histology. Given the rarity of this condition, the experience gained from the present case is a useful addition to the current knowledge on disease prognostication and management.A systematic review of the existing literature on PTC-NFS, including the case reported in the present paper, is also carried out, aiming to explore the patient characteristics and clinical behaviour pattern of this rare entity and to make appropriate recommendations on management strategy. The age of presentation ranges from 20 to 82 years, with a mean of 44.5 years. Female preponderance was observed, with a female to male ratio of 3ratio1. No racial predilection was observed. Tumour size varied from 2 to 9 cm along its greatest diameter (mean = 4.3 cm). Metastasis to lymph nodes at presentation occurred in 25 per cent of cases. Metastasis to surrounding structures (e.g. parathyroid and skeletal muscle) was observed in 12.5 per cent. There have been no reports of pulmonary or skeletal metastasis at presentation.
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PMID:Papillary thyroid carcinoma with exuberant nodular fasciitis-like stroma: treatment outcome and prognosis. 1662 82

Many histological variants of PTC have been described and some are known to have prognostic significance. However, their relative frequencies and associated clinicopathological features in a large cohort of patients with PTC treated at a single institution have seldom been documented. We reclassified 1035 malignant thyroid tumors treated in a 30-yr study period, into variants of PTC according to current histological criteria and analyzed their features. Six hundred and fifty two patients (153 men; 499 women) with PTC were identified. PTC accounted for 72.8% of primary thyroid cancers. Conventional papillary carcinoma (n = 300) accounted for 46% of PTC and papillary microcarcinoma 27.8% (n = 181). The frequencies of the common histological variants were follicular (17.6%, n =115), tall cell (4%, n = 26), and diffuse sclerosing (1.8%, n = 12). Uncommon histological variants including solid (n = 5), diffuse follicular (n = 5), papillary carcinoma with focal insular component (n = 3), columnar cell (n = 2), papillary carcinoma with fasciitis-like stroma (n = 2), and oncocytic (n = 1) were also noted. Histological variants of PTC had different age presentation, tumor size, frequencies of lymph node metastases, calcification, metaplastic bone, and psammoma bodies, when compared with conventional PTC. We conclude that a high prevalence of different variants of PTC with distinct clinicopathological features can be documented. Recognition of these histological variants may be important for better management of patients with PTC.
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PMID:Papillary carcinoma of thyroid: A 30-yr clinicopathological review of the histological variants. 1662 19

In summary, PTC is common, although it rarely results in disease-specific mortality. It is being diagnosed increasingly in the subclinical phase as a result of enhanced ultrasound imaging and more aggressive surveillance of smaller thyroid nodules. US-guided FNA is the "gold-standard" for diagnosis. Although controversy continues about the appropriate surgical management of PTC, total thyroidectomy is usually indicated given the frequent multicentricity and metastases of the disease, which in turn, necessitates adjuvant RAI and careful surveillance. An enhanced prognostic classification could better guide initial surgical therapy, standardize surveillance, and reduce the risk of recurrent and persistent disease. Research efforts should focus on the genetic and molecular underpinnings of PTC, as these would facilitate the identification of additional prognostic factors and potential targets for novel therapies.
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PMID:Papillary thyroid cancer. 1688 99

Papillary and follicular carcinomas, commonly referred to as follicular cell-derived differentiated thyroid carcinomas (DTC), account for 90% of all thyroid carcinomas. The prognosis of DTC is generally good, depending on the biologic behavior of the tumor and on the appropriate initial treatment which includes total thyroidectomy and ablation by radioiodine-131. However, a considerable number of patients, approximately 30%, as shown after 30 years of follow-up, have recurrent disease. It is thus of utmost importance to evaluate the prognostic factors, as derived from retrospective studies, and identify high risk patients. Age of more than 45 years or less than 25 years is a particularly strong independent prognostic factor; on the contrary gender is a poor prognostic factor. Histological type of the cancer especially tall cancer cells and columnar cancer cells, as well as increased vascular invasion of the tumor, lymph-node and distant metastases, are all considered as risk factors that can lead to poor prognosis. Combined prognostic factors have been used to form scoring systems (SS) such as AGES, MACIS, AMES, EORTC and TNM for a more precise description of high or low risk patients. However, prognostic significance of the SS is limited, since they do not take into consideration the clinical status or the treatment procedure during the course of the disease. Molecular factors such as rearrangements of genes RET/PTC, RAS mutations and fusion of, paired box and 8/peroxisome proliferator-activated receptor gamma (PAX8/PPARgamma) are also involved in thyroid cancer prognosis, while some others: human Pituitary- Tumor Transforming Gene (e.g. MIB-1, hPTTG) have been reported as additional prognostic factors. In this review we describe the risk and the prognostic factors of DTC as related to management and the outcome of DTC.
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PMID:Risk and prognostic factors for differentiated thyroid cancer. 1881 68

Approximately 10% of thyroid cancers are present in patients less than 21 years of age, representing 3% of all cancers of children and adolescents, with predominance in females 2:1 in relation to males. Thyroid cancers in this age group are usually papillary (90%), bilateral, multifocal and bigger in size compared to adults. Capsule invasion and lymphatic and pulmonary metastases are more frequent in children. Radiation sensitivity seems to represent an important factor in prepubertal patients. Familial history is reported in 5% of the cases. Genes such as RET/PTC, RAS and BRAF are usually involved in thyroid carcinogenesis in this age group. Cervical adenomegaly is a common clinical presentation, but does not represent a poor prognostic factor in children. Ultrasound and fine needle aspiration biopsy are valuable diagnostic procedures. Surgery is the preferred treatment including thyroidectomy and ganglionary excision, followed by ablative radioiodine therapy. L-thyroxine replacement with suppressive dosage should be employed targeting chronic TSH suppression. Long-term prognosis is usually better in children when compared with adults. Plasma thyroglobulin measurement is also useful to detect residual thyroid cancer disease.
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PMID:[Thyroid carcinoma in children and adolescents]. 1789 Dec 39

Since the 1980s, cancer cells have been considered to be derived from well-differentiated normal cells via multiple incidents of damage to their genome, especially in oncogenes or tumor suppressor genes, which accelerate proliferation or foster malignant phenotypes, such as the ability to invade the surrounding tissue or metastasize to distant organs. In the thyroid, a novel hypothesis of carcinogenesis, the "fetal cell carcinogenesis" hypothesis, in which thyroid cancer cells are derived from the remnants of fetal cells, instead of well-differentiated somatic cells, such as thyrocytes, by de-differentiation, is proposed. In this hypothesis, thyroid cancer cells are generated from three types of fetal thyroid cells, thyroid stem cells(TSCs), thyroblasts and prothyrocytes by proliferation without differentiation, which results in anaplastic, papillary and follicular carcinoma, respectively. Genomic alternations, such as RET/PTC and PAX8-PPARgamma1 rearrangements and a mutation in the BRAF gene, play an oncogenic role by preventing thyroid fetal cells from differentiating. This hypothesis well explains the clinical and biological features and recent molecular evidence of thyroid cancer. Further, it underscores the importance of identifying stem cells and clarifying the molecular mechanism of organ development. Such data will lead to better understanding of thyroid carcinogenesis and the establishment of more accurate diagnostic methods and more effective therapies. Analysis of molecular behavior in a single tumor cell will be a key technology in the future clinical pathology. Fetal cell science may be the leading research theme in the next few decades.
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PMID:[Fetal cell carcinogenesis hypothesis and its impact on clinical pathology of cancer]. 1854 90


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