Elsevier

Surgery

Volume 148, Issue 6, December 2010, Pages 1313-1315
Surgery

American Association of Endocrine Surgeon
Summary statement: Utility of molecular marker testing in thyroid cancer

Presented at the 29th Annual Meeting of the American Association of Endocrine Surgeons, Pittsburg, Pennsylvania, April 18-20, 2010.
https://doi.org/10.1016/j.surg.2010.09.023Get rights and content

The use of molecular markers for thyroid cancer diagnosis, prognosis, and surveillance have been an exciting area of study and change. Recent investigative focus on promising new markers will very likely lead to improvements in the diagnostic utility of fine needle aspiration biopsy (FNAB) in predicting malignancy, as well as provide more accurate prognostic information pre- and postoperatively. The 2010 Annual Meeting of the American Association for Endocrine Surgeons featured a symposium dedicated to molecular marker testing in thyroid cancer and its potential clinical applicability.

Section snippets

Diagnosis

Sonographic characterization and FNAB are recommended in the initial evaluation of thyroid nodules.1 FNAB is highly sensitive and is associated with only a 1–2% false-negative rate, but 20–30% of FNAB cytology results are indeterminate, requiring operative resection for a definitive diagnosis. Based on several promising studies, molecular markers can potentially improve the diagnostic accuracy of FNAB. This improvement has been shown by the analysis of a number of molecular markers of thyroid

Prognosis

As we are able to identify the molecular alterations seen with thyroid cancer, more information is emerging about the genotype-phenotype associations and prognosis. In follicular carcinoma, for example, fractional allelic loss, or quantification of the loss of heterozygosity, in a panel of tumor suppressor genes correlates with long-term survival in selected patients.11 In PTC, BRAFV600E is associated in most retrospective studies with histopathologic findings of aggressive disease such as

Surveillance

Measurement of serum thyroglobulin (Tg) levels remains the only blood test available for assessment of disease status in thyroid cancer patients undergoing long-term follow-up, and yet is unreliable for interpretation in 20% to 30% of patients because of Tg antibodies. Detection of TSHR mRNA in peripheral blood, however, has potential use as an additional postoperative indicator of persistent or recurrent thyroid cancer. A recent series of 119 patients with Tg antibodies or uninterpretable Tg

References (23)

  • M. Milas et al.

    The utility of peripheral thyrotropin mRNA in the diagnosis of follicular neoplasms and surveillance of thyroid cancers

    Surgery

    (2007)
  • L. Yip et al.

    Optimizing surgical treatment of papillary thyroid carcinoma associated with BRAF mutation

    Surgery

    (2009)
  • D.S. Cooper et al.

    Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer

    Thyroid

    (2009)
  • Y. Wang et al.

    Differentiating alternative splice variant patterns of human telomerase reverse transcriptase in thyroid neoplasms

    Thyroid

    (2008)
  • D.J. Finley et al.

    Discrimination of benign and malignant thyroid nodules by molecular profiling

    Ann Surg

    (2004)
  • E. Kebebew et al.

    Diagnostic and prognostic value of angiogenesis-modulating genes in malignant thyroid neoplasms

    Surgery

    (2005)
  • M.N. Nikiforova et al.

    Molecular diagnostics and predictors in thyroid cancer

    Thyroid

    (2009)
  • Y. Cohen et al.

    Mutational analysis of BRAF in fine needle aspiration biopsies of the thyroid: a potential application for the preoperative assessment of thyroid nodules

    Clin Cancer Res

    (2004)
  • G. Salvatore et al.

    Analysis of BRAF point mutation and RET/PTC rearrangement refines the fine-needle aspiration diagnosis of papillary thyroid carcinoma

    J Clin Endocrinol Metab

    (2004)
  • Y.E. Nikiforov et al.

    Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules

    J Clin Endocrinol Metab

    (2009)
  • S. Cantara et al.

    Impact of proto-oncogene mutation detection in cytological specimens from thyroid nodules improves the diagnostic accuracy of cytology

    J Clin Endocrinol Metab

    (2010)

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      Point mutations in BRAF and RAS (H-RAS, N-RAS, K-RAS) genes and gene rearrangements involving RET/PTC and PAX8/PPARγ have been studied extensively and identified in more than 70% of thyroid malignancies. Although these markers have a high positive predictive value and may serve as a useful adjunct to FNA in the future, current assays are still neither sensitive nor specific enough to differentiate benign from malignant follicular neoplasms.24–29 Conversely, a gene expression classifier (GEC) was developed to identify benign lesions among patients who have morphologically atypia of undetermined significance or suspicious for a follicular neoplasms on FNA.30

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      Recently, Nikiforov et al. showed that using a panel of markers to detect alterations in BRAF, RAS, PAX8/PPAR and RET/PTC can increase the overall accuracy of FNA (97%) compared to cytology alone [38]. This study has also showed that molecular testing when used in indeterminate cases increase the probability of cancer detection, however, only BRAFV600E mutation is a specific marker of PTC; nevertheless, the negativity for this mutation does not rule out this diagnosis [3,38,39]. Cytology offers a suitable alternative to biopsy in a variety of clinical settings and there are many studies showing the possibility of using cytological specimens to study response to therapy and evaluation of morphological changes of tumour cells with minimal discomfort for the patients.

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