Predictive Value of Somatic Mutations for the Development of Malignancy in Thyroid Nodules by Cytopathology

Csaba Halászlaki, Bálint Tóbiás, Bernadett Balla, J. Kósa, János Horányi, Eszter Bölöny, Zsolt Nagy, G. Speer, Balázs Járay, Eszter Székely, Roland Istók, Tamás Székely, Zsuzsanna Putz, Magdolna Dank, P. Lakatos, I. Takács

Research output: Contribution to journalArticle

Abstract

Objective: The purpose of our prospective longitudinal study was to evaluate the predictive efficacy of genetic testing for malignancies in fine-needle aspiration biopsy samples that are cytologically benign at the time of biopsy. Methods: A total of 779 aspirated cytological samples collected from thyroid nodules of 626 patients were included in a 3-year follow-up study. Consecutive patients with cytologically benign thyroid nodules by the Bethesda System for Reporting Thyroid Cytopathology were enrolled in the study. At enrollment, somatic 1-point nucleotide polymorphisms of BRAF and RAS family genes were tested by melting-point analysis, while RET/PTC and PAX8/PPAR-gamma rearrangements were examined by real-time polymerase chain reaction. The genetic test was considered to be positive if a somatic mutation was found. Malignant cytopathologic diagnoses were confirmed by histopathology. Results: In samples collected from 779 thyroid nodules, there were 39 BRAF, 33 RAS mutations, and 1 RET/PTC rearrangements found at the beginning of the study. No PAX8/PPAR-gamma rearrangement was identified. There were 52 malignant thyroid tumors removed during follow-up, out of which 24 contained a somatic mutation. The specificity of the presence of somatic mutations for malignancies was as high as 93.3%, and sensitivity was 46.2%. The negative predictive value of genetic testing reached 96.0%. Conclusion: Our results show that our set of genetic tests can predict the appearance of malignancy in benign thyroid nodules (at the beginning of follow-up) with high specificity and strong negative predictive value. Abbreviations: BRAF = v-raf murine sarcoma viral oncogene homolog B1 FLUS = follicular lesion of undetermined significance FNAB = fine-needle aspiration biopsy FTC = follicular thyroid carcinoma HRAS = homologous to the oncogene from the Harvey rat sarcoma virus KRAS = homologous to the oncogene from the Kirsten rat sarcoma virus NRAS = first isolated from a human neuroblastoma/neuroblastoma RAS = viral oncogene homolog PAX8 = paired box 8 PCR = polymerase chain reaction PPAR-gamma = peroxisome proliferator-activated receptor gamma PTC = papillary thyroid carcinoma RAS = rat sarcoma RET = rearranged during transfection tyrosine-kinase proto-oncogene SM = somatic mutation SNP = single-nucleotide polymorphism.

Original languageEnglish
Pages (from-to)1081-1087
Number of pages7
JournalEndocrine Practice
Volume22
Issue number9
DOIs
Publication statusPublished - Sep 1 2016

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Thyroid Nodule
PPAR gamma
Oncogenes
Factor IX
Mutation
Parvovirus
Genetic Testing
Neoplasms
Fine Needle Biopsy
Neuroblastoma
Sarcoma
Single Nucleotide Polymorphism
Harvey murine sarcoma virus
Thyroid Gland
Kirsten murine sarcoma virus
Follicular Adenocarcinoma
Polymerase Chain Reaction
Proto-Oncogenes
Protein-Tyrosine Kinases
Freezing

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Predictive Value of Somatic Mutations for the Development of Malignancy in Thyroid Nodules by Cytopathology. / Halászlaki, Csaba; Tóbiás, Bálint; Balla, Bernadett; Kósa, J.; Horányi, János; Bölöny, Eszter; Nagy, Zsolt; Speer, G.; Járay, Balázs; Székely, Eszter; Istók, Roland; Székely, Tamás; Putz, Zsuzsanna; Dank, Magdolna; Lakatos, P.; Takács, I.

In: Endocrine Practice, Vol. 22, No. 9, 01.09.2016, p. 1081-1087.

Research output: Contribution to journalArticle

Halászlaki, C, Tóbiás, B, Balla, B, Kósa, J, Horányi, J, Bölöny, E, Nagy, Z, Speer, G, Járay, B, Székely, E, Istók, R, Székely, T, Putz, Z, Dank, M, Lakatos, P & Takács, I 2016, 'Predictive Value of Somatic Mutations for the Development of Malignancy in Thyroid Nodules by Cytopathology', Endocrine Practice, vol. 22, no. 9, pp. 1081-1087. https://doi.org/10.4158/EP151057.OR
Halászlaki, Csaba ; Tóbiás, Bálint ; Balla, Bernadett ; Kósa, J. ; Horányi, János ; Bölöny, Eszter ; Nagy, Zsolt ; Speer, G. ; Járay, Balázs ; Székely, Eszter ; Istók, Roland ; Székely, Tamás ; Putz, Zsuzsanna ; Dank, Magdolna ; Lakatos, P. ; Takács, I. / Predictive Value of Somatic Mutations for the Development of Malignancy in Thyroid Nodules by Cytopathology. In: Endocrine Practice. 2016 ; Vol. 22, No. 9. pp. 1081-1087.
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AU - Horányi, János

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AU - Székely, Eszter

AU - Istók, Roland

AU - Székely, Tamás

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