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MiRNAs Are Involved in Tall Cell Morphology in Papillary Thyroid Carcinoma

1
Institute of Pathology, University of Bern, Murtenstrasse 31, CH 3008 Bern, Switzerland
2
Department of Pathology and Molecular Pathology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
3
Institute of Surgical Pathology, Stadtspital Triemli, Birmensdorferstr. 497, 8063 Zürich, Switzerland
4
Department of BioMedical Research, University of Bern, Murtenstrasse 31, CH 3008 Bern, Switzerland
5
Department of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(6), 885; https://doi.org/10.3390/cancers11060885
Received: 17 May 2019 / Revised: 13 June 2019 / Accepted: 14 June 2019 / Published: 25 June 2019
(This article belongs to the Special Issue Thyroid Cancer)
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Abstract

Five percent of papillary thyroid carcinomas (PTC) show an adverse clinical outcome (ACO). The tall cell variant of papillary thyroid carcinomas (TCV) is a good predictor of an ACO, however, the identification of tall-cells is subjective. Micro RNAs are short non-coding ribonucleic acids (miRNA). Their expression in PTC could be a powerful, more objective predictor of prognosis. Methods: Forty-four PTC underwent miRNA profiling, twenty-four of them were TCV. The miRNA dataset was validated by analysis of expression of known target proteins (vascular endothelial growth factor (VEGF) and phosphatase and tensin homolog (PTEN)) in 125 patients including 48 TCV and 57 with an ACO. Results: One hundred and forty-nine miRNAs were significantly associated with an ACO, seventy-one of them with TC-morphology. Twenty-two miRNAs were identified as targets for VEGF and thirty-two as targets for PTEN. In univariate and multivariable analysis, reduced expression of PTEN and an increased expression of VEGF were associated with shorter relapse free survival. A classifier, including TC-morphology, pT-stage, VEGF, and PTEN, predicted relapse with an 80% accuracy. Conclusions: Some miRNAs predict outcome in PTC and are involved in TC-morphology in PTC. These miRNAs may serve as more objective indicators of an ACO than tall cell morphology. PTEN and VEGF protein expression are prognostically relevant and are at least partially regulated by miRNAs. View Full-Text
Keywords: thyroid carcinoma; miRNA; PTEN; VEGF; prognosis; tall cell; TERT thyroid carcinoma; miRNA; PTEN; VEGF; prognosis; tall cell; TERT
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Boos, L.A.; Schmitt, A.; Moch, H.; Komminoth, P.; Simillion, C.; Marinoni, I.; Nikiforov, Y.E.; Nikiforova, M.N.; Perren, A.; Dettmer, M.S. MiRNAs Are Involved in Tall Cell Morphology in Papillary Thyroid Carcinoma. Cancers 2019, 11, 885.

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