Can the microRNA signature distinguish between thyroid tumors of uncertain malignant potential and other well-differentiated tumors of the thyroid gland?

The term ‘thyroid tumors of uncertain malignant potential’ (TT-UMP) was coined by surgical pathologists to define well-differentiated tumors (WDT) showing inconclusive morphological evidence of malignancy or benignity. We have analyzed the expression of microRNA (miRNA) in a training set of 42 WDT of different histological subtypes: seven follicular tumors of UMP (FT-UMP), six WDT-UMP, seven follicular thyroid adenomas (FTA), 11 conventional papillary thyroid carcinomas (C-PTC), five follicular variants of PTC (FV-PTC), and six follicular thyroid carcinomas (FTC), which led to the identification of about 40 deregulated miRNAs. A subset of these altered miRNAs was independently validated by qRT-PCR, which included 18 supplementary TT-UMP (eight WDT-UMP and ten FT-UMP). Supervised clustering techniques were used to predict the first 42 samples. Based on the four possible outcomes (FTA, C-PTC, FV-PTC, and FTC), about 80% of FTA and C-PTC and 50% of FV-PTC and FTC samples were correctly assigned. Analysis of the independent set of 18 WDT-UMP by quantitative RT-PCR for the selection of the six most discriminating miRNAs was unable to separate FT-UMP from WDT-UMP, suggesting that the miRNA signature is insufficient in characterizing these two clinical entities. We conclude that considering FT-UMP and WDT-UMP as distinct and specific clinical entities may improve the diagnosis of WDT of the thyroid gland. In this context, a small set of miRNAs (i.e. miR-7, miR-146a, miR-146b, miR-200b, miR-221, and miR-222) appears to be useful, though not sufficient per se, in distinguishing TT-UMP from other WDT of the thyroid gland.

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A Clinical Overview of Telomerase-Associated Aberrancies in Follicular Thyroid Tumors as Diagnostic and Prognostic Markers: Tert Alert!

Scandinavian Journal of Surgery ◽

10.1177/1457496919850434 ◽

2019 ◽

Vol 109 (3) ◽

pp. 187-192 ◽

Cited By ~ 1

Author(s):

C. C. Juhlin

Keyword(s):

Thyroid Cancer ◽

Reverse Transcriptase ◽

Malignant Potential ◽

Telomerase Reverse Transcriptase ◽

Thyroid Tumors ◽

Reverse Transcriptase Gene ◽

Thyroid Carcinomas ◽

Thyroid Adenomas ◽

Promoter Mutations ◽

Follicular Thyroid Tumors

Background and Aims: Endocrine surgeons and pathologists alike are well aware of the diagnostic predicament that follicular thyroid tumors impose in the clinical setting, best exemplified by the current inability to preoperatively assess the malignant potential of each individual lesion. As the proper recognition of a follicular thyroid carcinoma lies in the histopathological identification of invasive behavior, preoperative cytology alone is not yet sufficient to identify malignant tumors eligible for a total thyroidectomy upfront. Numerous auxiliary markers have been proposed as discriminating markers between follicular thyroid carcinomas and follicular thyroid adenomas, although many have proven suboptimal in terms of sensitivity, specificity, or overall clinical practicality. Of late, recurrent promoter mutations in the telomerase reverse transcriptase gene have been intimately coupled to subsets of well-differentiated thyroid cancer specimen with aggressive clinical characteristics as well as less differentiated forms of thyroid cancer with exceedingly poor prognosis. The mutations are thought to enhance the telomerase reverse transcriptase gene expressional output and cause immortalization through telomerase-associated mechanisms. Materials and Methods: In this review, the current value of telomerase reverse transcriptase promoter mutations is detailed from a clinical angle—as well as the possible future application of additional telomerase reverse transcriptase gene aberrations as adjunct markers for the proper recognition of malignant potential. Results: Telomerase reverse transcriptase promoter mutations are found in subsets of follicular thyroid carcinomas and follicular tumors of uncertain malignant potential while exceedingly rare in recurrence-free follicular thyroid adenomas. Collectively, these aberrancies are suggested as possible diagnostic and prognostic discriminators of follicular thyroid tumors. Conclusions: Telomerase reverse transcriptase gene analyses greatly facilitate the clinical assessment of follicular thyroid tumors, and pinpoints cases at risk of future recurrences. High-volume, tertiary thyroid centers are therefore recommended to implement the mutational screening in clinical routine.

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