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Background and Rationale: Anaplastic thyroid cancer (ATC) is characterized by pleomorphic cells, has a poor prognosis, is highly devastating disease, and is not curable. No reliable biomarkers of metastatic potential, helpful for early diagnosis of ATC and therapeutic response have been found yet. Thrombospondin-1 (TSP-1) plays a fundamental role in cancer progression by regulating cell stromal cross-talk in the tumor microenvironment. Goals: Our goal was to understand whether TSP-1 could affect protein levels of its integrin receptors (e.g., ITGα3, α6, and β1) and cell morphology in BRAFV600E-ATC cells in vitro and in vivo. Experimental Design: Anaplastic thyroid cancer-derived cell cultures and western blotting were used to assess integrin protein expression upon TSP-1 silencing. Immunohistochemistry was performed on orthotopic primary human ATC and metastatic ATC in lung tissue to compare TSP-1 and integrin protein expression levels. Results: TSP-1 knock-down down-regulates ITGα3, α6, and β1 in BRAFV600E-human ATC cells. BRAFV600E-ATC cells with TSP-1 knock-down were rounded compared to control cells, which displayed a spread morphology. TSP-1 knock-down also reduced TSP-1, ITGα3, α6, and β1 protein expression levels in vivo in the ATC microenvironment, which is enriched in stromal and inflammatory cells. Conclusion: TSP-1 silencing causes changes in ITG levels and ATC cell morphology. The assessment of TSP-1 and ITG levels might contribute to earlier metastatic potential of BRAFV600E-positive aggressive thyroid cancers, and allow improved patient selection for clinical trials. [ABSTRACT FROM AUTHOR]

Fine-needle aspiration biopsy is regarded as an important tool for diagnosing thyroid lesions because of its simplicity, safety, and cost-effectiveness. Its role in correctly characterizing the group of indeterminate lesions or follicular-patterned neoplasms (FN) might be more decisive. Liquid-based cytology (LBC) is a technique based on the use of a semi-automated device that has gained popularity as a method of collecting and processing both gynecologic and non-gynecologic cytologic specimens. It achieves a diagnostic sensitivity as accurate as conventional preparations especially for its excellent cell preservation and for the lack of background which decrease the amount of inadequate diagnoses. Moreover, the cellular material which has been stored in the preservative solution could be effectively used for the application of immunocytochemical and molecular techniques especially for the Follicular proliferations. In many cases the cytologic features are similar in both methods but the colloid film and the lymphocytic component are more easily evaluated on direct smears whereas nuclear details and colloid globules are better evaluated in LBC slides. The LBC-processed biopsies represent a valid alternative to conventional cytology. The possibility of applying special techniques enhance the efficacy of the cytological diagnosis of thyroid lesions. [ABSTRACT FROM AUTHOR]

RET gene rearrangements (RET/PTCs) represent together with BRAF point mutations the two major groups of mutations involved in papillary thyroid carcinoma (PTC) initiation and progression. In this review, we will examine the mechanisms involved in RET/PTC-induced thyroid cell transformation. In detail, we will summarize the data on the molecular mechanisms involved in RET/PTC formation and in its function as a dominant oncogene, on the activated signal transduction pathways and on the induced gene expression modifications. Moreover, we will report on the effects of RET/PTCs on the tumor microenvironment. Finally, a short review of the literature on RET/PTC prognostic significance will be presented. [ABSTRACT FROM AUTHOR]

Follicular cell-derived well-differentiated thyroid cancer, papillary (PTC) and follicular thyroid carcinomas comprise 95% of all thyroid malignancies. Familial follicular cell-derived well-differentiated thyroid cancers contribute 5% of cases. Such familial follicular cell-derived carcinomas or non-medullary thyroid carcinomas (NMTC) are divided into two clinical-pathological groups. The syndromic-associated group is composed of predominately non-thyroidal tumors and includes Pendred syndrome, Warner syndrome, Carney complex (CNC) type 1, PTEN-hamartoma tumor syndrome (PHTS; Cowden disease), and familial adenomatous polyposis (FAP)/Gardner syndrome. Other conditions with less established links to the development of follicular cell-derived tumors include ataxia-telangiectasia syndrome, McCune Albright syndrome, and Peutz-Jeghers syndrome. The final group encompasses syndromes typified by NMTC, as well as pure familial (f) PTC with or without oxyphilia, fPTC with multinodular goiter, and fPTC with papillary renal cell carcinoma. This heterogeneous group of diseases does not have the established genotype-phenotype correlations known as in the familial C-cell-derived tumors or medullary thyroid carcinomas (MTC). Clinicians should have the knowledge to identify the likelihood of a patient presenting with thyroid cancer having an additional underlying familial syndrome stemming from characteristics by examining morphological findings that would alert pathologists to recommend that patients undergo molecular genetic evaluation. This review discusses the clinical and pathological findings of patients with familial PTC, such as FAP, CNC, Werner syndrome, and Pendred syndrome, and the heterogeneous group of familial PTC. [ABSTRACT FROM AUTHOR]