Anaplastic thyroid cancer is an endocrine malignancy. Its rare and rapidly lethal disease course has made it challenging to study. Little is known regarding the expression by anaplastic tumors of ...molecular targets for new human anticancer agents that have been studied in the preclinical or clinical setting. The objective of this work was to evaluate the expression profile of anaplastic thyroid tumors for molecular targets for treatment.
Of the 94 cases of anaplastic thyroid cancers diagnosed and treated in British Columbia, Canada over a 20-year period (1984-2004), 32 cases (34%) had adequate archival tissue available for evaluation. A tissue microarray was constructed from these anaplastic thyroid tumors and immunohistochemistry was utilized to evaluate expression of 31 molecular markers. The markers evaluated were: epidermal growth factor receptor (EGFR), HER2, HER3, HER4, ER, PR, uPA-R, clusterin, E-cadherin, beta-catenin, AMF-R, c-kit, VEGF, ILK, aurora A, aurora B, aurora C, RET, CA-IX, IGF1-R, p53, MDM2, p21, Bcl-2, cyclin D1, cyclin E, p27, calcitonin, MIB-1, TTF-1, and thyroglobulin.
A single tumor with strong calcitonin expression was identified as a poorly differentiated medullary carcinoma and excluded from the study cohort. The mean age of the anaplastic cohort was 66 years; 16 patients (51%) were females, and the median patient survival was 23 weeks. A wide range in molecular marker expression was observed by the anaplastic thyroid cancer tumors (0-100%). The therapeutic targets most frequently and most strongly overexpressed by the anaplastic tumors were: beta-catenin (41%), aurora A (41%), cyclin E (67%), cyclin D1 (77%), and EGFR (84%).
Anaplastic thyroid tumors exhibit considerable derangement of their cell cycle and multiple signal transduction pathways that leads to uncontrolled cellular proliferation and the development of genomic instability. This report is the first to comprehensively evaluate a panel of molecular targets for therapy of anaplastic thyroid cancer and supports the development of clinical trials with agents such as cetuximab, small-molecule tyrosine kinase inhibitors, and aurora kinase inhibitors, which may offer new hope for individuals diagnosed with this fatal thyroid malignancy.
Anaplastic thyroid cancer arises, or transforms, from pre-existing differentiated thyroid cancer. E-cadherin functions as a cell–cell adhesion molecule that complexes with catenin proteins for ...function. The objective of this study was to evaluate the change in E-cadherin/β-catenin expression in the transformation of differentiated to anaplastic thyroid carcinoma.
A tissue microarray was constructed from 12 anaplastic thyroid tumors and their adjacent associated differentiated foci. Immunohistochemistry was used to evaluate tumor expression of E-cadherin and β-catenin.
There was decreased expression of E-cadherin and β-catenin by the anaplastic tumors when compared with the differentiated thyroid tumors from which they evolved. The expression of E-cadherin and β-catenin was 92% and 67%, respectively, by the differentiated thyroid carcinoma, and 17% and 50%, respectively, by the anaplastic tumors.
This report shows that derangement of the E-cadherin/catenin complex is associated with the transformation of differentiated into anaplastic thyroid carcinoma.
Formalin fixation is the standard method for the preservation of tissue for diagnostic purposes, including pathologic review and molecular assays. However, this method is known to cause artifacts ...that can affect the accuracy of molecular genetic test results. We assessed the applicability of alternative fixatives to determine whether these perform significantly better on next-generation sequencing assays, and whether adequate morphology is retained for primary diagnosis, in a prospective study using a clinical-grade, laboratory-developed targeted resequencing assay. Several parameters relating to sequencing quality and variant calling were examined and quantified in tumor and normal colon epithelial tissues. We identified an alternative fixative that suppresses many formalin-related artifacts while retaining adequate morphology for pathologic review.
An unusual cause of an incidental lung mass Lawson, Lindsay M; Tiwari, Pari; Filipenko, J Douglas
Canadian respiratory journal,
2003, Letnik:
10, Številka:
5
Journal Article
Recenzirano
Odprti dostop
A 52-year-old woman was found to have a mass measuring 1 cm in diameter with radiographic features of a carcinoid tumour in the left lung during work-up for chest pain. Wedge excision of the lesion ...revealed a leiomyoma that had a similar histological appearance to uterine 'fibroids' removed eight years previously. This case is an example of benign metastasizing leiomyoma, an unusual lesion of uncertain etiopathogenesis.
The impact of long-term changes in plasma viremia, produced by effective combination antiretroviral therapy, on human immunodeficiency virus (HIV) burden within tissue reservoirs is unknown. Fifteen ...patients who had received at least 1 year of therapy with two or three drug combinations of zidovudine, didanosine, and nevirapine had suitable samples of lymph node tissue obtained by ultrasound-guided core needle biopsy. HIV RNA was extracted fromhomogenized tissue samples and quantitated using a modified branched DNA assay. Results were correlated with antiretroviral treatment effect on the basis of plasma virus load measurements over the preceding 12–18 months. A statistically significant negative correlation was observed between magnitude of treatment effect on plasma viremia and lymph node virus load. These data suggest that combinations of antiretroviral drugs that produce sustained suppression of plasma HIV RNA may also be able to reduce the virus burden in lymphoid tissues.
Hürthle Cell Neoplasms of the Thyroid Maizlin, Zeev V.; Wiseman, Sam M.; Vora, Parag ...
Journal of ultrasound in medicine,
20/May , Letnik:
27, Številka:
5
Journal Article
Recenzirano
Objective. The purpose of this study was to determine the sonographic features of Hürthle cell neoplasms (HCNs) of the thyroid. Methods. We retrospectively analyzed the sonographic appearance of 15 ...histologically proven HCNs in 15 patients aged 16 to 70 years (mean age, 44 years). Sonographic features that were reviewed included the size and echogenicity of the tumors, the presence of cystic areas or calcifications, and detectable blood flow on color Doppler imaging. Correlation of sonographic findings with pathologic results was performed. Results. The tumors ranged from 0.4 to 7 cm in diameter, but most were less than 3 cm in diameter. Four (27%) of the 15 tumors were homogeneously hypoechoic. Two tumors (13%) were predominantly hypoechoic with isoechoic areas to thyroid parenchyma. Two (13%) neoplasms were isoechoic to thyroid parenchyma. Four (27%) tumors were predominantly isoechoic, containing hypoechoic areas, and 3 (20%) tumors were hyperechoic. Three neoplasms contained cystic components. None of the tumors contained calcifications. One tumor was avascular on Doppler examination. One neoplasm showed only peripheral blood flow. Thirteen tumors showed internal vascularity, 7 of them with peripheral blood flow. Twelve HCNs were benign, and 3 were malignant on pathologic examination. Conclusions. Hürthle cell neoplasms show a spectrum of sonographic appearances from predominantly hypoechoic to hyperechoic lesions and from peripheral blood flow with no internal flow to extensively vascularized lesions. Pathologic criteria differentiating benign and malignant HCNs (absence or presence of a capsular breach, vascular or extrathyroidal tissue invasion, nodal involvement, and distant metastasis) are beyond the resolution of sonography and fine‐needle aspiration biopsy and require removal of the entire lesion. This precludes diagnosis and characterization of HCNs by sonography.
The primary objective of this study was to determine the true proportion and optimal surgical approach for individuals undergoing thyroid operation for a suspicion of cancer based on a fine-needle ...aspiration biopsy diagnosis of a follicular neoplasm (FN). A secondary objective of this study was to determine whether patient characteristics could assist the clinician in predicting malignancy in this FN patient cohort.
A retrospective chart, pathology, and cytology review of 370 consecutive primary thyroid operations was performed over a 4-year period at a tertiary care referral center. Clinical patient data were evaluated as an adjunct for predicting malignancy in the FN patient cohort. Univariate and multivariate analyses were used to investigate the association and the predictability.
A total of 80 (22%) of the 370 patients underwent hemithyroidectomy to rule out cancer based on clinical presentation with a fine-needle aspiration biopsy diagnosis of FN. Fifteen (19%) of the FN cases were diagnosed as cancer by histological analysis (4 follicular carcinomas and 11 papillary carcinomas). Hemithyroidectomy was considered adequate treatment for 77 patients (96%). No patient characteristic significantly predicted the presence of cancer by either univariate or multivariate analysis.
Overall, in the FN patient population, five hemithyroidectomies were performed to identify each cancer, and no further operation was required in 96% of patients. New diagnostic tools are needed to reduce the number of operations performed for benign pathology in patients with nodular thyroid disease and a needle biopsy diagnosis of FN.
The purpose of this study was to determine the sonographic features of Hürthle cell neoplasms (HCNs) of the thyroid.
We retrospectively analyzed the sonographic appearance of 15 histologically proven ...HCNs in 15 patients aged 16 to 70 years (mean age, 44 years). Sonographic features that were reviewed included the size and echogenicity of the tumors, the presence of cystic areas or calcifications, and detectable blood flow on color Doppler imaging. Correlation of sonographic findings with pathologic results was performed.
The tumors ranged from 0.4 to 7 cm in diameter, but most were less than 3 cm in diameter. Four (27%) of the 15 tumors were homogeneously hypoechoic. Two tumors (13%) were predominantly hypoechoic with isoechoic areas to thyroid parenchyma. Two (13%) neoplasms were isoechoic to thyroid parenchyma. Four (27%) tumors were predominantly isoechoic, containing hypoechoic areas, and 3 (20%) tumors were hyperechoic. Three neoplasms contained cystic components. None of the tumors contained calcifications. One tumor was avascular on Doppler examination. One neoplasm showed only peripheral blood flow. Thirteen tumors showed internal vascularity, 7 of them with peripheral blood flow. Twelve HCNs were benign, and 3 were malignant on pathologic examination.
Hürthle cell neoplasms show a spectrum of sonographic appearances from predominantly hypoechoic to hyperechoic lesions and from peripheral blood flow with no internal flow to extensively vascularized lesions. Pathologic criteria differentiating benign and malignant HCNs (absence or presence of a capsular breach, vascular or extrathyroidal tissue invasion, nodal involvement, and distant metastasis) are beyond the resolution of sonography and fine-needle aspiration biopsy and require removal of the entire lesion. This precludes diagnosis and characterization of HCNs by sonography.
A subset of patients with colon cancer staged by conventional methods have occult micrometastases and do not receive adjuvant chemotherapy. Sentinel lymph node (SLN) mapping and staining by ...immunohistochemistry is a technique that may identify such occult micrometastases, thereby upstaging patients with positive findings. The purpose of this study was to determine whether ex vivo SLN mapping in colon cancer could be applied successfully to patients at our institution.
Seventeen patients with intraperitoneal colon tumors undergoing resection were studied prospectively. SLNs were identified as the first blue stained node(s) after ex vivo peritumoral injection of isosulfan blue dye. Additional lymph nodes were harvested and processed in accordance with standard pathologic evaluation for colon cancer. All nodes were examined after routine hematoxylin and eosin (H&E) staining. SLNs that were negative on H&E were analyzed further by multilevel sectioning and immunohistochemistry staining using anticytokeratin monoclonal antibody.
Of the 17 study patients, SLNs were identified in 16 (94%) cases. The SLN was the only positive node in 3 patients. An identified SLN was positive (by H&E) in all patients with associated positive non-SLN nodes. The average number of nodes retrieved per patient was 16 (range, 4–54). Overall, SLNs accurately reflected the status of the entire lymph node basin in 16 (94%) patients. Two (12%) patients with negative nodes by H&E potentially were upstaged after further SLN analysis. The negative predictive value for SLN mapping was 89%.
The ex vivo technique of SLN mapping for colon cancer is feasible. In the current study, SLN results were concordant with non-SLNs in the majority of patients. Furthermore, this technique may have upstaged 2 (12%) patients. Whether this ultimately will affect overall survival has yet to be determined.
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