Real-time PCR cycle threshold values for the BRAFV600E mutation in papillary thyroid microcarcinoma may be associated with central lymph node metastasis

A retrospective study

Vivian Y. Park, Eunkyung Kim, Hye Sun Lee, Hee Jung Moon, Jung Hyun Yoon, jinyoung kwak

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Papillary thyroid microcarcinoma (PTMC) usually has excellent prognosis, but a small subset shows aggressive behavior. Although the B-Raf proto-oncogene, serine/threonine kinase (BRAF)V600E mutation is the most common oncogenic alteration in PTMCs, it is frequently heterogeneously distributed within tumors. The aim of this study was to investigate the association of the BRAFV600E mutation found in fine needle aspirates from PTMCs with known clinicopathologic prognostic factors, based on both its presence and a quantitative approach that uses cycle threshold (Ct) values obtained by a real-time PCR technique. The 460 PTMC patients were included, with 367 patients having the BRAFV600E mutation. Clinicopathologic variables were compared between patients with and without the BRAFV600E mutation. BRAFV600E Ct values were compared according to clinicopathologic prognostic factors. Multivariate analyses were performed to evaluate factors predicting extrathyroidal extension and central and lateral lymph node metastasis (LNM). Each analysis used either the BRAFV600E mutation status or the Ct value as an independent variable for all the study patients and the 367 BRAFV600E-positive patients. Receiveroperating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of BRAFV600E Ct values in predicting central and lateral LNM. The BRAFV600E mutation statuswas not associated with clinicopathologic prognostic factors among the 460 PTMC patients. Of the 367 BRAFV600E-positive patients, Ct values were significantly lower in patients with central and lateral LNM (P<0.001, P=0.007). The Ct value was the only independent factor to predict central LNM(OR 0.918, P=0.025). The area under the ROC curve (AUC) for diagnosing central LNMwas 0.623 (sensitivity, 50.0%; specificity, 71.9%) and for diagnosing lateral LNM, it was 0.796 (sensitivity, 71.4%; specificity, 94.7%). In conclusion, real-time PCR Ct values for the BRAFV600E mutation obtained from fine needle aspirates can be associatedwith centralLNMin PTMC patients. Although BRAFV600E Ct values did not reach statistical significance for predicting lateral LNM in our study, further validation through larger studies can be used to overcome any possible type-II errors. With further studies,Ct values for the BRAFV600E mutation obtained from fine needle aspirates may have important implications for predicting both central and lateral LNM in patients with PTMCs.

Original languageEnglish
Article numbere1149
JournalMedicine (United States)
Volume94
Issue number28
DOIs
Publication statusPublished - 2015 Jul 1

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Real-Time Polymerase Chain Reaction
Retrospective Studies
Lymph Nodes
Neoplasm Metastasis
Mutation
Needles
Papillary Thyroid Microcarcinoma
Proto-Oncogenes
Validation Studies
Protein-Serine-Threonine Kinases
Multivariate Analysis

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

@article{a9c9bb98903a4f77acc3a48c24dff21c,
title = "Real-time PCR cycle threshold values for the BRAFV600E mutation in papillary thyroid microcarcinoma may be associated with central lymph node metastasis: A retrospective study",
abstract = "Papillary thyroid microcarcinoma (PTMC) usually has excellent prognosis, but a small subset shows aggressive behavior. Although the B-Raf proto-oncogene, serine/threonine kinase (BRAF)V600E mutation is the most common oncogenic alteration in PTMCs, it is frequently heterogeneously distributed within tumors. The aim of this study was to investigate the association of the BRAFV600E mutation found in fine needle aspirates from PTMCs with known clinicopathologic prognostic factors, based on both its presence and a quantitative approach that uses cycle threshold (Ct) values obtained by a real-time PCR technique. The 460 PTMC patients were included, with 367 patients having the BRAFV600E mutation. Clinicopathologic variables were compared between patients with and without the BRAFV600E mutation. BRAFV600E Ct values were compared according to clinicopathologic prognostic factors. Multivariate analyses were performed to evaluate factors predicting extrathyroidal extension and central and lateral lymph node metastasis (LNM). Each analysis used either the BRAFV600E mutation status or the Ct value as an independent variable for all the study patients and the 367 BRAFV600E-positive patients. Receiveroperating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of BRAFV600E Ct values in predicting central and lateral LNM. The BRAFV600E mutation statuswas not associated with clinicopathologic prognostic factors among the 460 PTMC patients. Of the 367 BRAFV600E-positive patients, Ct values were significantly lower in patients with central and lateral LNM (P<0.001, P=0.007). The Ct value was the only independent factor to predict central LNM(OR 0.918, P=0.025). The area under the ROC curve (AUC) for diagnosing central LNMwas 0.623 (sensitivity, 50.0{\%}; specificity, 71.9{\%}) and for diagnosing lateral LNM, it was 0.796 (sensitivity, 71.4{\%}; specificity, 94.7{\%}). In conclusion, real-time PCR Ct values for the BRAFV600E mutation obtained from fine needle aspirates can be associatedwith centralLNMin PTMC patients. Although BRAFV600E Ct values did not reach statistical significance for predicting lateral LNM in our study, further validation through larger studies can be used to overcome any possible type-II errors. With further studies,Ct values for the BRAFV600E mutation obtained from fine needle aspirates may have important implications for predicting both central and lateral LNM in patients with PTMCs.",
author = "Park, {Vivian Y.} and Eunkyung Kim and Lee, {Hye Sun} and Moon, {Hee Jung} and Yoon, {Jung Hyun} and jinyoung kwak",
year = "2015",
month = "7",
day = "1",
doi = "10.1097/MD.0000000000001149",
language = "English",
volume = "94",
journal = "Medicine (United States)",
issn = "0025-7974",
publisher = "Lippincott Williams and Wilkins",
number = "28",

}

Real-time PCR cycle threshold values for the BRAFV600E mutation in papillary thyroid microcarcinoma may be associated with central lymph node metastasis : A retrospective study. / Park, Vivian Y.; Kim, Eunkyung; Lee, Hye Sun; Moon, Hee Jung; Yoon, Jung Hyun; kwak, jinyoung.

In: Medicine (United States), Vol. 94, No. 28, e1149, 01.07.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Real-time PCR cycle threshold values for the BRAFV600E mutation in papillary thyroid microcarcinoma may be associated with central lymph node metastasis

T2 - A retrospective study

AU - Park, Vivian Y.

AU - Kim, Eunkyung

AU - Lee, Hye Sun

AU - Moon, Hee Jung

AU - Yoon, Jung Hyun

AU - kwak, jinyoung

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Papillary thyroid microcarcinoma (PTMC) usually has excellent prognosis, but a small subset shows aggressive behavior. Although the B-Raf proto-oncogene, serine/threonine kinase (BRAF)V600E mutation is the most common oncogenic alteration in PTMCs, it is frequently heterogeneously distributed within tumors. The aim of this study was to investigate the association of the BRAFV600E mutation found in fine needle aspirates from PTMCs with known clinicopathologic prognostic factors, based on both its presence and a quantitative approach that uses cycle threshold (Ct) values obtained by a real-time PCR technique. The 460 PTMC patients were included, with 367 patients having the BRAFV600E mutation. Clinicopathologic variables were compared between patients with and without the BRAFV600E mutation. BRAFV600E Ct values were compared according to clinicopathologic prognostic factors. Multivariate analyses were performed to evaluate factors predicting extrathyroidal extension and central and lateral lymph node metastasis (LNM). Each analysis used either the BRAFV600E mutation status or the Ct value as an independent variable for all the study patients and the 367 BRAFV600E-positive patients. Receiveroperating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of BRAFV600E Ct values in predicting central and lateral LNM. The BRAFV600E mutation statuswas not associated with clinicopathologic prognostic factors among the 460 PTMC patients. Of the 367 BRAFV600E-positive patients, Ct values were significantly lower in patients with central and lateral LNM (P<0.001, P=0.007). The Ct value was the only independent factor to predict central LNM(OR 0.918, P=0.025). The area under the ROC curve (AUC) for diagnosing central LNMwas 0.623 (sensitivity, 50.0%; specificity, 71.9%) and for diagnosing lateral LNM, it was 0.796 (sensitivity, 71.4%; specificity, 94.7%). In conclusion, real-time PCR Ct values for the BRAFV600E mutation obtained from fine needle aspirates can be associatedwith centralLNMin PTMC patients. Although BRAFV600E Ct values did not reach statistical significance for predicting lateral LNM in our study, further validation through larger studies can be used to overcome any possible type-II errors. With further studies,Ct values for the BRAFV600E mutation obtained from fine needle aspirates may have important implications for predicting both central and lateral LNM in patients with PTMCs.

AB - Papillary thyroid microcarcinoma (PTMC) usually has excellent prognosis, but a small subset shows aggressive behavior. Although the B-Raf proto-oncogene, serine/threonine kinase (BRAF)V600E mutation is the most common oncogenic alteration in PTMCs, it is frequently heterogeneously distributed within tumors. The aim of this study was to investigate the association of the BRAFV600E mutation found in fine needle aspirates from PTMCs with known clinicopathologic prognostic factors, based on both its presence and a quantitative approach that uses cycle threshold (Ct) values obtained by a real-time PCR technique. The 460 PTMC patients were included, with 367 patients having the BRAFV600E mutation. Clinicopathologic variables were compared between patients with and without the BRAFV600E mutation. BRAFV600E Ct values were compared according to clinicopathologic prognostic factors. Multivariate analyses were performed to evaluate factors predicting extrathyroidal extension and central and lateral lymph node metastasis (LNM). Each analysis used either the BRAFV600E mutation status or the Ct value as an independent variable for all the study patients and the 367 BRAFV600E-positive patients. Receiveroperating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of BRAFV600E Ct values in predicting central and lateral LNM. The BRAFV600E mutation statuswas not associated with clinicopathologic prognostic factors among the 460 PTMC patients. Of the 367 BRAFV600E-positive patients, Ct values were significantly lower in patients with central and lateral LNM (P<0.001, P=0.007). The Ct value was the only independent factor to predict central LNM(OR 0.918, P=0.025). The area under the ROC curve (AUC) for diagnosing central LNMwas 0.623 (sensitivity, 50.0%; specificity, 71.9%) and for diagnosing lateral LNM, it was 0.796 (sensitivity, 71.4%; specificity, 94.7%). In conclusion, real-time PCR Ct values for the BRAFV600E mutation obtained from fine needle aspirates can be associatedwith centralLNMin PTMC patients. Although BRAFV600E Ct values did not reach statistical significance for predicting lateral LNM in our study, further validation through larger studies can be used to overcome any possible type-II errors. With further studies,Ct values for the BRAFV600E mutation obtained from fine needle aspirates may have important implications for predicting both central and lateral LNM in patients with PTMCs.

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DO - 10.1097/MD.0000000000001149

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JO - Medicine (United States)

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