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Exp Clin Endocrinol Diabetes 2016; 124(03): 198-202
DOI: 10.1055/s-0035-1565061
Article
© Georg Thieme Verlag KG Stuttgart · New York

Genetic Alterations in Differentiated Thyroid Cancer Patients with Acromegaly

K. Aydin
1   Department of Endocrinology and Metabolism, Hacettepe University School of Medicine, Ankara, Turkey
,
C. Aydin
2   Department of Pathology, Hacettepe University School of Medicine, Ankara, Turkey
,
S. Dagdelen
1   Department of Endocrinology and Metabolism, Hacettepe University School of Medicine, Ankara, Turkey
,
G. G. Tezel
2   Department of Pathology, Hacettepe University School of Medicine, Ankara, Turkey
,
T. Erbas
1   Department of Endocrinology and Metabolism, Hacettepe University School of Medicine, Ankara, Turkey
› Author Affiliations
Further Information

Publication History

received 03 July 2015
first decision 13 September 2015

accepted 30 September 2015

Publication Date:
17 November 2015 (online)

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Abstract

Aim: Acromegaly is associated with increased thyroid cancer risk. We aimed to analyze the frequency of point mutations of BRAF and RAS genes, and RET/PTC, PAX8/PPARγ gene rearrangements in patients with acromegaly having differentiated thyroid cancers (DTC) and their relation with clinical and histological features.

Materials and Methods: 14 acromegalic patients (8 male, 6 female) with DTC were included. BRAF V600E and NRAS codon 61 point mutations, RET/PTC1, RET/PTC3, and PAX8/PPARγ gene rearrangements were analyzed in thyroidectomy specimens. We selected 14 non-acromegalic patients with DTC as a control group.

Results: 2 patients (14.3%) were detected to have positive BRAF V600E and 3 patients (21.4%) were detected to have NRAS codon 61 mutation. NRAS codon 61 was the most frequent genetic alteration. Patients with positive mutation had aggressive histologic features more frequently than patients without mutations. Comparison of the acromegalic and non-acromegalic patients with DTC revealed that BRAF V600E mutation was more frequent in non-acromegalic patients with DTC (14.2% vs. 64.3%, p=0.02). RET/PTC 1/ 3, PAX8/PPARγ gene rearrangements were not detected in any patient. None of the patients including the patients with positive point mutations had recurrence, and local and/or distant metastasis.

Conclusion: NRAS codon 61 is the most frequent genetic alteration in this acromegaly series with DTC. Since acromegalic patients have lower prevalance of BRAF V600E mutation, BRAF V600E mutation may not be a causative factor in development of DTC in acromegaly. Despite the relation of BRAF V600E and NRAS codon 61 mutations with aggresive histopathologic features, their impact on tumor prognosis remains to be defined in acromegaly in further studies.

Key words

acromegaly - thyroid cancer - BRAF - NRAS - genetic alteration
 

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