Nuclear-specific accumulation of () mRNA in promoter mutated follicular thyroid tumours visualised by in situ hybridisation: a possible clinical screening tool?

AIMS

Upregulation of the () gene is a frequent finding in follicular thyroid carcinomas (FTCs) with metastatic features. The augmented expression is usually caused by promoter mutations. As TERT protein immunohistochemistry might not correlate to mRNA levels in follicular thyroid tumours, we therefore sought to determine if visualisation of 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 promoter mutations and gene expression, as well as 16 FTCs with no gene aberrancy or gene expression, and assessed them using RNA Scope in situ hybridisation (ISH) and probes targeting the two main transcripts ().

RESULTS

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

CONCLUSIONS

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