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Mutant-specific BRAF and CD117 immunocytochemistry potentially facilitate risk stratification for papillary thyroid carcinoma in fine-needle aspiration biopsy specimens

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Tumor Biology

Abstract

The study aims to test whether combination of mutant-specific BRAF and CD117 immunocytochemical (ICC) staining stratifies probability for papillary thyroid carcinoma (PTC) in thyroid fine-needle aspiration biopsy (FNAB) specimens. A consecutive cohort of cases diagnosed as atypia of undetermined significance (AUS) or suspicious for malignancy-suspicious for papillary thyroid carcinoma (SM-SPTC) from 30 December, 2011 to 23 October, 2014 in a single institute was enrolled. Forty cytologically benign and 50 cytologically diagnosed PTC within the same time span were also included. CD117 and mutant-specific BRAF (BRAF VE1) ICC staining was performed. Association of BRAF VE1 and CD117 expression with final diagnosis was analyzed. Both BRAF VE1 and CD117 showed good performance in distinguishing PTC from benign nodules. Combination of BRAF VE1 and CD117 stratified 180 cases into three categories: BRAF VE1 positive regardless of CD117 expression (ICC-malignant), BRAF VE1 negative plus low level of CD117 expression (ICC-intermediate), and BRAF VE1 negative plus high level of CD117 expression (ICC-benign), which was associated with 100, 75.6, and 0 % of malignancy. Combination of mutant-specific BRAF and CD117 ICC may potentially facilitate the PTC risk stratification in FNAB thyroid nodule specimens.

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References

  1. Cibas ES, Ali SZ. The Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol. 2009;132(5):658–65.

    Article  PubMed  Google Scholar 

  2. Jo VY et al. Malignancy risk for fine-needle aspiration of thyroid lesions according to the Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol. 2010;134(3):450–6.

    Article  PubMed  Google Scholar 

  3. Eszlinger, M., et al. (2015) Molecular testing of thyroid fine needle aspirations (FNA) improves pre-surgical diagnosis and supports the histological identification of minimally invasive follicular thyroid carcinomas. Thyroid.

  4. Hyeon J et al. The prediction of malignant risk in the category “atypia of undetermined significance/follicular lesion of undetermined significance” of the Bethesda system for reporting thyroid cytopathology using subcategorization and BRAF mutation results. Cancer Cyto Pathol. 2014;122(5):368–76.

    Article  CAS  Google Scholar 

  5. Capper D et al. Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. Acta Neuropathol. 2011;122(1):11–9.

    Article  CAS  PubMed  Google Scholar 

  6. Prasad NB et al. Identification of genes differentially expressed in benign versus malignant thyroid tumors. Clin Cancer Res. 2008;14(11):3327–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rosen J et al. A six-gene model for differentiating benign from malignant thyroid tumors on the basis of gene expression. Surgery. 2005;138(6):1050–6. discussion 1056-7.

    Article  PubMed  Google Scholar 

  8. Pusztaszeri MP, Sadow PM, Faquin WC. CD117: a novel ancillary marker for papillary thyroid carcinoma in fine-needle aspiration biopsies. Cancer Cyto Pathol. 2014;122(8):596–603.

    Article  CAS  Google Scholar 

  9. Tomei S et al. c-KIT receptor expression is strictly associated with the biological behaviour of thyroid nodules. J Transl Med. 2012;10:7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chen GY YX, Liu J, You QH, Zhou XG. A novel cell block technique for fine needle aspiration biopsy samples. Zhonghua Bing Li Xue Za Zhi. 2011;40(8):558–9.

    PubMed  Google Scholar 

  11. Xing M et al. Detection of BRAF mutation on fine needle aspiration biopsy specimens: a new diagnostic tool for papillary thyroid cancer. J Clin Endocrinol Metab. 2004;89(6):2867–72.

    Article  CAS  PubMed  Google Scholar 

  12. Xing M et al. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA. 2013;309(14):1493–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Diggans J et al. Machine learning from concept to clinic: reliable detection of braf v600e DNA mutations in thyroid nodules using high-dimensional RNA expression data. Pac Symp Biocomput. 2015;20:371–82.

    Google Scholar 

  14. Dvorak K et al. Immunohistochemistry with the anti-BRAF V600E (VE1) antibody: impact of pre-analytical conditions and concordance with DNA sequencing in colorectal and papillary thyroid carcinoma. Pathology. 2014;46(6):509–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zimmermann AK et al. Value of immunohistochemistry in the detection of BRAF(V600E) mutations in fine-needle aspiration biopsies of papillary thyroid carcinoma. Cancer Cyto Pathol. 2014;122(1):48–58.

    Article  CAS  Google Scholar 

  16. Lu J et al. Association between BRAF V600E mutation and regional lymph node metastasis in papillary thyroid carcinoma. Int J Clin Exp Pathol. 2015;8(1):793–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Saggiorato E et al. Characterization of thyroid ‘follicular neoplasms’ in fine-needle aspiration cytological specimens using a panel of immunohistochemical markers: a proposal for clinical application. Endocr Relat Cancer. 2005;12(2):305–17.

    Article  CAS  PubMed  Google Scholar 

  18. Saleh HA et al. Differential expression of galectin-3, CK19, HBME1, and Ret oncoprotein in the diagnosis of thyroid neoplasms by fine needle aspiration biopsy. Cyto J. 2009;6:18.

    Google Scholar 

  19. Cochand-Priollet B et al. Immunocytochemistry with cytokeratin 19 and anti-human mesothelial cell antibody (HBME1) increases the diagnostic accuracy of thyroid fine-needle aspirations: preliminary report of 150 liquid-based fine-needle aspirations with histological control. Thyroid. 2011;21(10):1067–73.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Zhiyong Liang.

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Zhilan Meng and Junliang Lu contributed equally to the present study.

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Meng, Z., Lu, J., Wu, H. et al. Mutant-specific BRAF and CD117 immunocytochemistry potentially facilitate risk stratification for papillary thyroid carcinoma in fine-needle aspiration biopsy specimens. Tumor Biol. 37, 611–618 (2016). https://doi.org/10.1007/s13277-015-3837-9

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  • DOI: https://doi.org/10.1007/s13277-015-3837-9

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