Biomedical subjects

Mariwil Wong

Publications and source records attributed to Mariwil Wong.

9 recordsLinked to original sources

PubMed2006

Does familial non-medullary thyroid cancer adversely affect survival?

BACKGROUND: Familial non-medullary thyroid cancer (FNMTC) is associated with a higher rate of multifocality and a higher recurrence rate than sporadic thyroid cancer. However, the effect of FNMTC on life expectancy is unknown. MATERIAL AND METHODS: Using data from our FNMTC database, we calculated life expectancy and survival rates after diagnosis of FNMTC and compared the results with the rates for unaffected family members and for the standard US population. Overall life expectancy and survival rates were calculated using the Kaplan-Meier method. We compared patients from families with 2 affected members with patients from families with > or = 3 affected members. We also compared patients diagnosed in a known familial setting (index cases and subsequent cases) with patients diagnosed before the familial setting was recognized. RESULTS: There were 139 affected patients with 757 unaffected family members. The mean age at diagnosis was 40.8 +/- 13.9 years and the mean follow-up time was 9.4 +/- 11.7 years. Ten patients died of thyroid cancer during follow-up. The life expectancy of patients with FNMTC was similar to that of their unaffected family members. Survival was significantly shorter for patients with 3 or more affected family members, for patients diagnosed before the familial setting was recognized, and for patients with anaplastic cancer. CONCLUSIONS: Our results suggest that FNMTC may be more aggressive than sporadic thyroid cancer, particularly in families with 3 or more affected members. However, when recognized and treated appropriately, it does not significantly shorten the overall life expectancy of the affected patients.

Adenocarcinoma, Follicular↗

PubMed2006

Differentiated thyroid cancer cell invasion is regulated through epidermal growth factor receptor-dependent activation of matrix metalloproteinase (MMP)-2/gelatinase A.

Mechanisms of invasion in thyroid cancer remain poorly understood. We hypothesized that signaling via the epidermal growth factor receptor (EGFR) stimulates thyroid cancer cell invasion by altering the expression and cleavage of matrix metalloproteinases (MMPs). Papillary and follicular carcinoma cell lines were treated with EGF, the EGFR tyrosine kinase inhibitor AG1478, and the MMP inhibitors GM-6001 and Col-3. Flow cytometry was used to detect EGFR. In vitro invasion assays, gelatin zymography, and quantitative reverse transcription-PCR were used to assess the changes in invasive behavior and MMP expression and activation. All cell lines were found to overexpress functional EGFR. EGF stimulated invasion by thyroid cancer cells up to sevenfold (P<0.0001), a process that was antagonized completely by AG1478 and Col-3, partially by GM-6001, but not by the serine protease inhibitor aprotinin. EGF upregulated expression of MMP-9 (2.64- to 8.89-fold, P<0.0001) and membrane type-1 MMP (MT1-MMP, 1.97- to 2.67-fold, P<0.0001). This effect was blocked completely by AG1478 and partially by Col-3. The activation of MMP-2 paralleled MT1-MMP expression. We demonstrate that MMPs are critical effectors of invasion in the papillary and follicular thyroid cancer cell lines studied. Invasion is regulated by signaling through EGFR, an effect mediated by augmentation of gelatinase expression and activation. MMP inhibitors and growth factor antagonists may be effective tumoristatic agents for the treatment of aggressive thyroid carcinomas.

Adenocarcinoma, Follicular↗

PubMed2005

Glucose transporters in the thyroid.

Glucose transport, mediated by proteins expressed from the glucose transporter genes, plays an essential role in cellular metabolism. Increased uptake of glucose compared to cells in normal tissue is a defining characteristic of malignant cells. This has been the basis for positron emission tomography imaging of thyroid tumor metastases using fluorodeoxyglucose uptake. Despite this key difference between tumor and normal cells, the mechanism which mediates increased glucose uptake is poorly understood. Several research studies have assessed the expression of different glucose transporter (GLUT) proteins and expression of the genes which code for them in thyroid tissues. While no consensus exists on the specifics of which GLUT genes or proteins are expressed, a picture has emerged that a single specific transporter, GLUT1, is expressed at higher levels in thyroid carcinomas compared to a variety of normal and nonmalignant forms of thyroid disease. Greater levels of GLUT1 expression may be associated with poorer prognosis. Experiments in established thyroid carcinoma cells lines may provide useful insights into glucose transport in the thyroid. Thyroid cells show increased glucose uptake in response to thyroid-stimulating hormone (TSH), but expression of GLUT genes does not appear to be significantly affected by TSH suggesting TSH affects glucose uptake by affecting GLUT localization/ translocation rather than through increased GLUT gene expression. Improving technologies are providing a stronger foundation for detailed analyses of glucose transporters in thyroid to better elucidate the mechanisms by which these genes and proteins are regulated in normal and pathogenic tissue.

Glucose Transport Proteins, Facilitative↗

PubMed2004

Follicular thyroid carcinoma: histology and prognosis.

BACKGROUND: Follicular thyroid carcinoma (FTC) is the second most common thyroid malignancy after papillary thyroid carcinoma. The authors studied the clinical course of 132 patients with FTC to determine whether there was a direct relation between the histologic degree of invasion, tumor recurrence, and patient survival. METHODS: The 132 patients in the study population underwent 182 thyroid carcinoma-related operations, and their mean follow-up was 7.5 years (median:,6 years; range, 0-39 years). The following criteria were used to define malignant follicular neoplasms: 1) minimally invasive, tumor invasion through the entire thickness of the tumor capsule; 2) moderately invasive, tumor with angioinvasion (with or without capsular invasion); and 3) widely invasive, broad area or areas of transcapsular invasion of thyroid and extrathyroidal tissue. Forty-five of 119 patients (37.8%) presented with minimally invasive FTC (capsular invasion only), 50 patients (42%) presented with moderately invasive FTC (angioinvasion with or without capsular invasion), and 24 patients (20%) presented with widely invasive FTC. At presentation, 12 patients (9%) had distant metastases, and 8 patients (6%) had lymph node metastases. RESULTS: Excluding 12 patients who presented with distant metastases, 21 patients (16%) developed recurrent metastases 6 months after their initial treatment. Among 45 patients with capsular invasion only, 6 patients (13%) developed recurrent or persistent disease, and 5 patients (11%) died. Of the 50 patients who had angioinvasion with or without capsular invasion, 10 patients (20%) developed recurrent or persistent disease, and 7 patients (14%) died. Patients who had angioinvasion with or without capsular invasion had a less favorable prognosis compared with patients who had capsular invasion only (P < 0.0001). Among patients who had widely invasive FTC, 9 of 24 patients (38%) developed recurrent disease, and 8 patients (33%) died; in addition, 7 of the other 24 patients (29%) had persistent disease and died. The overall death rate for patients with widely invasive FTC was 62%. Patients with persistent disease had a poorer prognosis compared with patients who had recurrent disease (P < 0.0001). Twenty-eight patients (21%) in the entire group died of FTC. CONCLUSIONS: In the current retrospective investigation, the authors demonstrate that patients with minimally invasive FTC (capsular invasion only) had a slightly better survival rate at 5 years (98%) compared with patients who had angioinvasion with or without capsular invasion (80%) and had better survival compared with patients who had widely invasive FTC (38%). Other (but not all) reports in the literature support the findings that FTC with angioinvasion is more aggressive than FTC with only capsular invasion yet is less aggressive than widely invasive FTC. The authors conclude that FTC no longer should be classified as either minimally invasive or widely invasive; rather, they recommend classifying FTC as minimally invasive, moderately invasive, or widely invasive, because prognosis varies according to these groupings.

Adenocarcinoma, Follicular↗

PubMed2003

Anaplastic thyroid cancer: cytogenetic patterns by comparative genomic hybridization.

We studied chromosomal abnormalities by comparative genomic hybridization (CGH) and flow cytometry in anaplastic thyroid cancer (ATC), and when present in coexisting or previous differentiated thyroid cancer (DTC). Overall 10 frozen tissues from patients with ATC and 5 cell lines (1 ATC and 4 DTCs) were analyzed. We found chromosomal abnormalities in 5 of 10 ATC tissues, with 24 abnormalities (22 gains and 2 losses). Among 8 ATCs that were associated with prior or concurrent DTC, more chromosomal abnormalities were found in ATC associated with follicular thyroid cancer (FTC) than those associated with PTC (median numbers 9.5 and 0.5, respectively, p = 0.046) or no associated differentiated thyroid cancer. Gain of 1q was relatively common in ATCs (30%). By flow cytometry, we found aneuploidy in 6 of 10 ATC tissues and diploidy in 4. There was concordance between DNA aneuploidy and the presence of chromosomal abnormalities by CGH in 4 of the 5 ATCs (p = 0.048). We also found 26 chromosomal abnormalities in an ATC cell line, 14.3 in 3 FTC cell line, and 3 in a PTC cell line. In conclusion, chromosomal abnormalities are frequent in ATCs associated with FTC, but uncommon in those associated with PTC and in ATCs with no associated differentiated thyroid cancer. These findings support the concept that PTC and FTC have different genetic backgrounds and, even after the transformation to ATC, they may retain some of their cytogenetic characteristics.

Adenocarcinoma, Follicular↗

PubMed2003

Chromosomal aberrations by comparative genomic hybridization in thyroid tumors in patients with familial nonmedullary thyroid cancer.

PURPOSE: Nonmedullary thyroid cancer is the most common form of thyroid cancer and its familial form (FNMTC) is increasingly recognized as a distinct clinical entity. However, the genetic background of FNMTC is still poorly understood and the causative gene(s) have not yet been identified. METHODS: Because comparative genomic hybridization allows for screening of the entire tumor genome simultaneously for chromosomal gains and/or losses without prior knowledge of potential aberrations, we used this technique in thyroid normal and neoplastic samples from FNMTC patients (1) to analyze whether chromosomal aberrations would correlate with inheritance pattern, and/or clinicopathologic features and (2) to compare comparative genomic hybridization (CGH) findings in familial tumors with those already known in sporadic differentiated thyroid cancers. RESULTS: No common germline or somatic chromosomal aberrations were observed in patients with FNMTC because the frequencies and most locations of chromosomal aberrations in familial tumors were also common in sporadic tumors. However, some somatic aberrations were only found in familial tumors (gains in 2q, 3q, 18p, and 19p). Common aberrations in familial tumors corresponded to several locations of candidate genes already reported for sporadic thyroid tumorigenesis. CONCLUSIONS: Our findings suggest that chromosomal aberrations in thyroid tumors in patients with FNMTC are not related to inheritance pattern but rather to tumorigenesis.

Adolescent↗

PubMed2003

HER2 expression in thyroid tumors.

Similarities exist in hormone receptors of breast, prostate, and thyroid tumors. HER2 oncogene expression is known to be present in breast and prostate tumors, but conflicting data have been published about its presence in thyroid tumors. This uncertainty prompted us to examine the incidence of HER2 overexpression in normal and malignant thyroid tissue. Normal and neoplastic thyroid tissue samples from 46 female and 9 male patients were assayed for HER2 expression by immunohistochemical assay. Of the 55 total samples, 36 were from neoplasms and 19 were from benign tissues. Significant HER2 overexpression was not found in any benign or malignant thyroid tissue. Two of 6 thyroid carcinomas from male patients showed 1+ reactivity for HER2 expression on immunohistochemistry assay, but remained negative on fluorescene in sito hybridization confirmatory testing. No significant expression of HER2 was noted in benign or malignant thyroid tissue. These results cast doubt on the value of HER2 as a prognostic factor or possible target for specific antitumor therapy for thyroid cancer.

Adolescent↗

PubMed2002

Genetic screening for MEN1 mutations in families presenting with familial primary hyperparathyroidism.

A large number of families with familial isolated hyperparathyroidism (FIHP) have been reported. We wanted to determine if some of these families represent early manifestations of full-blown syndromes such as multiple endocrine neoplasia type 1 (MEN-1), as early identification may alter surgical and medical management. Four small families with a family history of hyperparathyroidism without clear-cut MEN-1 features were screened for a MEN1 mutation. The 10 exons of the MEN1 gene were amplified and analyzed by single-strand conformation analysis (SSCA). Abnormal SSCA shifts were then sequenced using an automated sequencer. Two germline mutations were found: R527X and P277H. The former was detected in three members of a family consisting of two children and a mother. At the time of testing the youngest son was normocalcemic and clinically normal but subsequently developed hyperparathyroidism (HPT). Since the initial testing, the family has been confirmed to be a MEN-1 family as the mother has developed abdominal pain and an elevated serum pancreatic polypeptide and the younger brother an anterior pituitary tumor and recurrent HPT. The latter P277H mutation was identified in two of three members tested from another family. Manifestations of MEN-1 syndrome have also developed. The father now has developed diarrhea and elevated serum gastrin; and the daughter has developed recurrent HPT. Genetic screening of families who clinically have FIHP is important and may influence the type of medical and surgical treatment and follow-up, as some have MEN-1 syndrome. Long-term screening for MEN syndromes should be included in this set of patients. Positive screening may predict disease and allow early detection and appropriate treatment before initiation of symptoms.

Adolescent↗

PubMed2002

Increasing the effectiveness of radioactive iodine therapy in the treatment of thyroid cancer using Trichostatin A, a histone deacetylase inhibitor.

BACKGROUND: Radioactive iodine is used to identify and treat recurrent and metastatic thyroid cancer of follicular cell origin. Between 30% and 40% of thyroid cancers are either resistant or become resistant to radioactive iodine. Increased sodium-iodide symporter (NIS) and decreased Pendrin (PDS) activity may be associated with increased radioactive iodine effectiveness. In this investigation the effects of Trichostatin A (TSA), a histone deacetylating inhibitor, on human thyroid NIS and PDS gene expression was investigated. METHOD: Cell lines from papillary, Hürthle, and follicular cell carcinomas were treated with TSA for 72 hours at concentrations up to 100 ng/mL. NIS and PDS gene expression was determined using quantitative RT-polymerase chain reaction. RESULTS: . NIS messenger RNA expression in cell carcinomas was increased 107- (1.8-307) and 217- (5.7-408) fold in papillary, 39- (20-63) and 58- (37-80) fold in Hürthle, and 459- (178-810) and 781- (412-1229) fold in follicular after treatment with 50 and 100 ng/mL of TSA, respectively. PDS messenger RNA expression in cell carcinomas was decreased 0.22- (0.05-0.45) and 0.27- (0.09-0.47) fold in papillary, 0.53- (0.46-0.60) and 0.54- (0.44-0.64) fold in Hürthle, and 0.32- (0.26-0.39) and 0.56- (0.47-0.64) fold in follicular, after the same treatment. CONCLUSIONS: In thyroid cancer cell lines, TSA dramatically increased NIS gene expression and reduced PDS expression. The increased NIS expression and reduced PDS expression may make radioiodine therapy more effective in patients with thyroid cancer, especially when the tumors have no or low uptake of radioiodine.

Carcinoma, Papillary↗