Analysis of differential BRAFV600E mutational status in multifocal papillary thyroid carcinoma

Evidence of independent clonal origin in distinct tumor foci

Authors

  • So Yeon Park MD,

    1. Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea
    2. Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
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  • Young Joo Park MD,

    1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea
    2. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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  • Yu Jin Lee MD,

    1. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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  • Hyun Sook Lee BS,

    1. Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
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  • Sung Hee Choi MD,

    1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea
    2. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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  • Gheeyoung Choe MD,

    1. Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea
    2. Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
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  • Hak-Chul Jang MD,

    1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea
    2. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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  • Seong Hoe Park MD,

    1. Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
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  • Do Joon Park MD,

    Corresponding author
    1. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
    2. Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
    • Department of Internal Medicine, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea
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    • Fax: (011) 82-2-762-9662

  • Bo Youn Cho MD

    1. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
    2. Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
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Abstract

BACKGROUND.

Papillary thyroid cancers often occur as multiple foci. Multifocal cancers have been considered to have a poor prognosis because they are thought to be the consequence of intrathyroidal spread of the papillary cancer. However, to the authors' knowledge there has been little investigation into whether multifocal thyroid papillary carcinomas arise from the intrathyroidal spread of a single carcinoma or from independent primary tumors. To answer this question, the BRAFV600E mutational status of individual tumor foci was examined. This approach was justified because in the Korean population a high proportion (65%) of papillary carcinomas harbor the BRAF mutation.

METHODS.

DNA was isolated from paraffin-embedded tissue samples of multifocal papillary thyroid carcinoma and the BRAF exon 15 was amplified by the polymerase chain reaction (PCR). The PCR product was digested with restriction endonuclease TspRI to test for the presence of the BRAFV600E (T1799A) mutation.

RESULTS.

In all, 140 cancers from 61 patients diagnosed with multifocal papillary carcinoma were examined. The BRAF mutation was found in all the individual cancers in 29 (47.5%) of the patients (all-positive group) and the mutation was absent in all the individual cancers in 8 (13.1%) patients (all-negative group). However, in 24 (39.3%) patients, some of the individual cancers contained the BRAF mutation, whereas others did not (mixed group).

CONCLUSIONS.

At least 39.3% of the multifocal papillary cancers in the Korean population that were examined could be attributed to independently arising papillary cancers rather than to intrathyroidal spread of single cancers. Cancer 2006. © 2006 American Cancer Society.

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