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RET/PTC1 Rearrangement in Hashimoto Thyroiditis

Canonical WNT Expression Up-regulation for Neoplastic Promotion

Al-Hashimi, Fatima, MD, FRCPath; Diaz-Cano, Salvador J., MD, PhD, FRCPath

doi: 10.1097/PCR.0000000000000289
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Background More than half a century has passed since the association between papillary thyroid carcinoma (PTC), and Hashimoto thyroiditis (HT) has been described. The discovery of the RET/PTC oncogene 30 years later has further strengthened this argument, followed by the associations made between hyalinizing trabecular adenoma (HTA) and both PTC and HT. Numerous researchers studied these relationships, with some debating a valid link.

Findings This case of a 28-year-old woman with HT-associated PTC and a coexisting HTA offers a unique opportunity to study these three lesions together in the same microenvironment. Fresh tissue analysis for gene expression showed that all three expressed RET/PTC1 transcripts, whereas this was not seen in the control normal thyroid tissue. There was also an increased expression of AKT, ERK1, nuclear β-catenin, and TCF4 in both the HTA and PTC sampled tissue. AKT plays a central role in regulating cell proliferation and survival by inhibiting apoptotic processes, whereas ERK1 leads to cell proliferation. Both β-catenin and TCF4 are linked to the canonical WNT/β-catenin pathway.

Conclusions The expression of RET/PTC1 highlights the link between inflammatory processes such as HT and neoplastic conditions such as HTA and PTC. The limited expression of TCF4, AKT, ERK1, and β-catenin supports the notion that the canonical WNT/β-catenin pathway plays a pivotal role in the development of this neoplasm. It is important to note that at this time, gene expression alone is not sufficient to make a distinction between benign and malignant thyroid lesions.

From the Department of Pathology, Salmaniya Medical Complex, Bahrain and King's College Hospital—King's Health Partners, London, United Kingdom.

Reprints: Salvador J. Diaz-Cano, MD, PhD, FRCPath, Department of Histopathology, King's College Hospital, Denmark Hill London, Greater London, United Kingdom SE5 9RS. E-mail: sdiaz-cano@nhs.net.

The authors have no funding or conflicts to declare.

The protocol used in the study was approved by the Hospital Research Board and Ethical Committees and complied with their requirements.

Author Contributions: Conceived and designed the study: S.D.C. Performed the experiments and statistical analysis, analyzed and interpreted the data, drafted the manuscript, revised the manuscript critically for important intellectual content, and authors read and approved the final manuscript: FH, S.D.C.

© 2019 Lippincott Williams & Wilkins, Inc.