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Nuclear-specific accumulation of telomerase reverse transcriptase (TERT) mRNA in TERT promoter mutated follicular thyroid tumours visualised by in situ hybridisation: a possible clinical screening tool?
  1. L Samuel Hellgren1,2,
  2. Ann Olsson2,
  3. Ann Kaufeldt2,
  4. Johan O Paulsson1,
  5. Martin Hysek1,2,
  6. Adam Stenman3,4,
  7. Jan Zedenius3,4,
  8. Catharina Larsson1,
  9. Anders Höög1,2,
  10. C Christofer Juhlin1,2
  1. 1Department of Oncology–Pathology, Karolinska Institutet, Stockholm, Sweden
  2. 2Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden
  3. 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
  4. 4Department of Breast, Endocrine Tumors and Sarcoma, Karolinska University Hospital, Stockholm, Sweden
  1. Correspondence to Dr C Christofer Juhlin, Department of Pathology and Cytology, Radiumhemmet, P1:02, Karolinska University Hospital Solna, 17176, Stockholm, Sweden; christofer.juhlin{at}ki.se

Abstract

Aims Upregulation of the telomerase reverse transcriptase (TERT) gene is a frequent finding in follicular thyroid carcinomas (FTCs) with metastatic features. The augmented expression is usually caused by TERT promoter mutations. As TERT protein immunohistochemistry might not correlate to TERT mRNA levels in follicular thyroid tumours, we therefore sought to determine if visualisation of TERT mRNA through in situ hybridisation could highlight high-risk cases.

Methods We collected formalin-fixated paraffin-embedded tissues from 26 follicular thyroid tumours; 7 FTCs, 2 follicular thyroid tumours of uncertain malignant potential (FT-UMPs) and a single Hürthle cell carcinoma with established TERT promoter mutations and gene expression, as well as 16 FTCs with no TERT gene aberrancy or gene expression, and assessed them using RNA Scope in situ hybridisation (ISH) and TERT probes targeting the two main TERT transcripts (TERT1 and TERT2).

Results TERT 1 and/or 2 mRNA was found by ISH in 8/10 cases with established promoter mutations and mRNA expression, whereas all 16 cases without TERT gene aberrancies or gene expression were negative (Fisher’s exact p<0.001). Strikingly, TERT mRNA was visualised in the nuclear compartment only, thereby corroborating earlier studies suggesting a non-conventional role for TERT in tumour biology. Moreover, TERT mRNA expression was scattered across the tissue sections and only found in a few percentages of tumour nuclei.

Conclusions TERT mRNA seems to be focally expressed and localised exclusively to the nucleus in TERT promoter mutated follicular thyroid tumours, possibly reflecting a true biological and unorthodox phenomenon worthy of further investigations.

  • in situ hybridization
  • thyroid neoplasms
  • pathology
  • molecular

Data availability statement

All data relevant to the study are included in the article. The authors confirm that the data supporting the findings of this study are available within the article.

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Data availability statement

All data relevant to the study are included in the article. The authors confirm that the data supporting the findings of this study are available within the article.

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Footnotes

  • Handling editor Runjan Chetty.

  • Contributors Conceived and designed the experiments: LSH, AO, AK, AH, CCJ. Performed the experiments: AO, AK. Analysed the data: LSH, AO, AK, JOP, MH, AS, JZ, CL, AH, CCJ. Wrote the paper: LSH, CCJ.

  • Funding This study was financially supported by grants generously provided by the Swedish Cancer Society, the Swedish Society for Medical Research and the Stockholm City Council.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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