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Keywords:

  • thyroid papillary carcinoma;
  • liquid-based cytology;
  • BRAF mutation;
  • prognostic parameters

BACKGROUND

Activating mutations in the valine-to-glutamic acid substitution at position 600 of the v-raf murine sarcoma viral oncogene homolog B1 (BRAF-1) gene are detected frequently in patients with papillary thyroid carcinoma (PTC). These mutations have been identified in approximately 29% to 69% of PTCs and in >80% of PTCs of the tall cell variant, whereas they have not been detected in benign lesions or in the majority of those (80%) with the follicular variant of PTC. The objective of the current study was to evaluate the role of liquid-based cytology (LBC) for the detection of BRAF mutations in the outcome of patients who have thyroid PTC measuring ≤1 cm and, hence, in guiding their clinical and surgical management.

METHODS

From October 2010 through June 2011, 230 consecutive cases were diagnosed as positive for malignancy on fine-needle aspiration cytology processed by LBC. Of these, 73 PTCs ≤1 cm underwent BRAF mutational analysis. The aspirated material was processed using an LBC technique. After DNA extraction of the residual material, BRAF mutation analysis was performed using a direct sequencing method.

RESULTS

Fifty of 73 patients (68.5%) underwent surgery, and 34 of those patients (68%) had tumors that expressed a BRAF mutation (31 PTCs, including 11 tall cell variants and 3 follicular-variant PTCs). A significant association between BRAF mutation and bilaterality of cancer was observed (odds ratio, 0.077; P = .0007). BRAF mutation was associated significantly with lymph node involvement (odds ratio, 19; P = .0007) but not with extracapsular infiltration (odds ratio, 0.298; P = .179).

CONCLUSIONS

The current results indicated that BRAF gene mutations can be identified successfully on LBC material and using other cytologic methods with high reproducibility, feasibility, and informative results. The presence of a BRAF mutation may preoperatively predict the behavior of microscopic PTC, suggesting a more aggressive surgical approach. Cancer (Cancer Cytopathol) 2013;121:291–7. © 2012 American Cancer Society.