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Clonal analysis of early-stage bilateral papillary thyroid cancer identifies field cancerization

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Abstract

Introduction

Bilaterality is a newly identified indicator for aggressive tumor behavior and poor outcome in papillary thyroid cancer. However, the clonal origin of these bilateral tumors remains unclear.

Methods

Here we analyzed 28 pairs of early-stage papillary thyroid cancers (stage I–II without extra-thyroidal extension, lymph node metastasis or distant metastasis) that underwent surgery at First Affiliated Hospital of Zhejiang University School of Medicine (Hangzhou, China). Genomic DNA was extracted from paraffin-embedded tissues after microdissection and analyzed for BRAF mutation and X-chromosome inactivation.

Results

A total of 16 patients (16/28, 57.1%) harbored different BRAF status in bilateral tumors. Fourteen patients were available for X-chromosome inactivation assay and 10 of them achieved informative results. Bilateral tumors from four cases had distinct patterns of X-chromosome inactivation. Combining the results of X-chromosome inactivation and BRAF analysis, we demonstrated that at least 64.3% (18/28) cases harbored discordant X-chromosome inactivation or BRAF status, indicating their independent clonal origin in bilateral tumors.

Conclusions

The present study confirms “field cancerization” in early-stage bilateral thyroid cancers, suggesting that these subtype papillary thyroid cancers should be treated as independent and localized tumors.

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Acknowledgements

This study is supported by Grants from National Natural Science Foundation of China (No. 81202141, and 81272676), the Key Project of Scientific and Technological Innovation of Zhejiang Province (No. 2015C03G2010206), National Science and Technology Major Project of the Ministry of Science and Technology of China (No. 2013ZX09506015), Medical Science and Technology Project of Zhejiang Province (No. 2011ZDA009), and Natural Science Foundation of Zhejiang Province (No. Y2110414).

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Author notes

  1. These authors contributed equally: Xingyun Su, Shitu Chen

Authors and Affiliations

  1. Cancer Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

    Xingyun Su, Shitu Chen, Kuifeng He, Zhuochao Mao, Jiaying Ruan, Weibin Wang & Lisong Teng

  2. Department of Pathology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

    Jie Zhou & Xiaodong Teng

  3. Department of Endocrine Surgery, Cleveland Clinic, Cleveland, OH, USA

    Judy Jin

  4. Department of Surgery, New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, NY, USA

    Thomas J. Fahey III

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  1. Xingyun Su
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Correspondence to Weibin Wang or Lisong Teng.

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This study was approved by the Institutional Review Board of First Affiliated Hospital, Zhejiang University School of Medicine. Informed consent has been obtained from each patient after full explanation of the purpose and nature of all procedures were used according to the Helsinki Declaration of 1975, as revised in 1983.

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Su, X., Chen, S., He, K. et al. Clonal analysis of early-stage bilateral papillary thyroid cancer identifies field cancerization. Endocrine 64, 614–621 (2019). https://doi.org/10.1007/s12020-019-01877-1

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