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A stem cell role for thyroid solid cell nests.

José Cameselle-Teijeiro·Ana Preto·Paula Soares·Manuel Sobrinho-Simões
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Carcinoma, PapillaryCell DifferentiationCell LineageCell Transformation, NeoplasticHumansStem CellsThyroid GlandThyroid NeoplasmsCommentLetter

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José Cameselle-Teijeiro, Ana Preto, Paula Soares, Manuel Sobrinho-Simões. 2005. A stem cell role for thyroid solid cell nests.. https://doi.org/10.1016/j.humpath.2005.02.010

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PubMed2006

RET/papillary thyroid cancer rearrangement in nonneoplastic thyrocytes: follicular cells of Hashimoto's thyroiditis share low-level recombination events with a subset of papillary carcinoma.

CONTEXT: RET/papillary thyroid cancer (PTC) is a marker for papillary thyroid carcinoma, but its specificity has been questioned because of the disputed identification of RET/PTC in Hashimoto's thyroiditis (HT), oncocytic tumors, and other thyroid lesions. OBJECTIVE: The objective of this study was to determine 1) whether RET/PTC occurs in nonneoplastic follicular cells of HT, and 2) its recombination rate in thyroid tumors. DESIGN/PATIENTS: Forty-three samples from 31 cases of HT were examined using interphase fluorescence in situ hybridization (FISH) with RET probes spanning the breakpoint region; real-time RT-PCR to quantify RET/PTC1, RET/PTC3, and c-RET transcripts; and RT-PCR after laser capture microdissection to enrich samples for follicular cells. The results were compared with those similarly obtained in 34 papillary carcinomas, eight thyroid oncocytic tumors, and 21 normal thyroids. RESULTS: Normal samples showed no RET rearrangement. Sixty-eight percent (15 of 22) of HT were positive by FISH; in all thyroiditis, signals were localized to rare nonneoplastic follicular cells; low-level RET/PTC was identified in 17% (five of 29) of thyroiditis cases by real-time RT-PCR and in an additional six of 11 real-time negative cases after increasing sensitivity with laser capture microdissection. Low RET/PTC1 levels were detected in 26% (nine of 34) of papillary carcinomas with an expression pattern and proportion of FISH-positive cells similar to those of the thyroiditis. Forty-seven percent (16 of 34) of papillary carcinomas and one oncocytic carcinoma expressed high RET/PTC1 mRNA levels. CONCLUSIONS: Low-level RET/PTC recombination occurs in nonneoplastic follicular cells in HT and in a subset of papillary thyroid carcinomas. RET/PTC expression variability should be taken into account for the molecular diagnosis of thyroid lesions. Overlapping molecular mechanisms may govern early stages of tumor development and inflammation in the thyroid.

Carcinoma, Papillary↗
PubMed2006

Lymphadenectomy for papillary thyroid cancer: changes in practice over four decades.

AIMS: Lymphadenectomy in the management of papillary thyroid cancer (PTC) has evolved. The aim of this study was to examine the changing role of neck dissection as reflected in the practice of a large thyroid unit over four decades. METHODS: A retrospective cohort study of patients that underwent primary thyroid surgery for papillary cancer in a single unit in the period 1958-2002. Nine 5-year periods were considered and the data relevant to the treatment of the regional lymph nodes reviewed. RESULTS: Nine hundred patients with PTC underwent surgery between 1958 and 2002 of whom 32.7% underwent lymph node dissection (LND). The use of lymphadenectomy increased from 21.4% in 1958-1962 to 48.1% in 1998-2002 of which 84% underwent a selective lymph node dissection (SLND)-a dissection where the LND is determined by the extent of the disease encountered. The mean number of nodes removed during SLND was 12.6 (range 1-56) of which a mean of 3.1 (24.8%) (0-19) were involved by the disease. Cervical levels 6 and level 4 were those most frequently dissected. There was no statistically significant difference in the complication rates in patients undergoing neck dissection and those not. CONCLUSION: The four decade experience reflects a move away from modified radical neck dissection and cherry picking towards SLND. Growing evidence suggests that lymphadenopathy in adult PTC is an adverse prognostic factor. SLND, a lymphadenectomy tailored to the extent of the disease process, is the coherent treatment for PTC since it serves the dual purpose of staging as well as control of local disease. This can be achieved with little morbidity when performed in a specialist centre.

Carcinoma, Papillary↗
PubMed2006

Simulated weightlessness changes the cytoskeleton and extracellular matrix proteins in papillary thyroid carcinoma cells.

Studies of astronauts, experimental animals, and cells have shown that, after spaceflights, the function of the thyroid is altered by low-gravity conditions. The objective of this study was to investigate the cytoskeleton and extracellular matrix (ECM) protein synthesis of papillary thyroid cancer cells grown under zero g. We investigated alterations of ONCO-DG 1 cells exposed to simulated microgravity on a three-dimensional random-positioning machine (clinostat) for 30 min, 24 h, 48 h, 72 h, and 120 h (n=6, each group). ONCO-DG 1 cells grown under microgravity exhibited early alterations of the cytoskeleton and formed multicellular spheroids. The cytoskeleton was disintegrated, and nuclei showed morphological signs of apoptosis after 30 min. At this time, vimentin was increased. Vimentin and cytokeratin were highly disorganized, and microtubules (alpha-tubulin) did not display their typical radial array. After 48 h, the cytoskeletal changes were nearly reversed. The formation of multicellular spheroids continued. In parallel, the accumulation of ECM components, such as collagen types I and III, fibronectin, chondroitin sulfate, osteopontin, and CD44, increased. The levels of both transforming growth factor beta-1 (TGF-beta(1)) and TGF-beta receptor type II proteins were elevated from 24 h until 120 h clinorotation. Gene expression of TGF-beta(1) was clearly enhanced during culture under zero g. The amount of E-cadherin was enhanced time-dependently. We suggest that simulated weightlessness rapidly affects the cytoskeleton of papillary thyroid carcinoma cells and increases the amount of ECM proteins in a time-dependent manner.

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