[358] The Combination of HBME-1 and Galectin-3 with BRAF-1 Mutation on Liquid-Based Cytology Identifies High-Risk Follicular Thyroid Lesions

Guido Fadda, Esther D Rossi, Maurizio Martini, Gian Franco Zannoni, Valerio G Vellone, Celestino P Lombardi, Alfredo Pontecorvi, Luigi M Larocca, Guido Rindi. Universita' Cattolica, Rome, Italy

Background: Thyroid nodules are common findings in adults, but only few of them are malignant. Fine needle aspiration cytology (FNAC) is the most important tool for evaluating these lesions which may yield an indeterminate diagnosis (Follicular Neoplasm – FN). To decrease the FN diagnoses, mutations of BRAF gene and immunocytochemistry (ICC) for HBME-1 and Galectin-3 have been studied. BRAF-1 mutations involving the V600E locus have been identified in as much as 70% of classic and tall cell (TCV) variants of PC and are regarded as useful in improving the specificity of the FNAC. They have not been detected in benign lesions and in the majority (80%) of the follicular variants of PTC. This study focuses on the combination of an ICC panel (HBME-1 and Galectin-3) with BRAF mutation for refining the indeterminate cytologic (including atypical cells of undetermined significance – AUS – and FN) and suspicious for carcinoma (SC) diagnoses.
Design: Among 34 FNAB processed by LBC, 9 were FN (including AUS) and 25 were SC. The ICC expression of HBME-1 and Galectin-3 and the BRAF V600E mutation were investigated with the ThinPrep 2000 (Hologic Co, Marlborough MA) technique. Immunocytochemical staining were carried out with the avidin-biotin peroxidase complex on LBC slides. The DNA extraction for the mutational analysis was performed on the same LBC material using the QIAamp tissue kit (Qiagen, Hilden, Germany) with the PCR amplification of the exon 11.
Results: Seven FN/AUS and 15 SC underwent surgery. In the surgical series 7 positive BRAF cases and 9 ICC positive cases were found. The results are shown in the Tables

Table 1: BRAF-1 mutation analysis on 22 surgical patients
SURGICAL SERIESFOLLICULAR NEOPL. (INCL. AUS)SUSPICIOUS FOR CARCINOMA
 BRAF+BRAF-BRAF+BRAF-
BENIGN0308
PTC/TCV0060
FVPTC0410
PTC/TCV (papillary thyroid carcinoma/tall cell variant) FVPTC (follicular variant of papillary carcinoma)



Table 2: Immunocytochemical expression of HBME-1 and Galectin-3 on 16 surgical cases
SURGICAL SERIESFOLLICULAR NEOPL. (INCL. AUS)SUSPICIOUS FOR CARCINOMA
 ICC +ICC -ICC +ICC -
BENIGN0311
PTC/TCV0060
FVPTC1310



Conclusions: BRAF-1 mutations and expression of HBME-1 and Galectin-3 on LBC enhance the accuracy of FNA in detecting thyroid malignancy. ICC seems to be more effective in identifying malignancies in lesions with indeterminate cytology (FN/AUS) whereas BRAF-1 mutation analysis discovers more carcinomas in suspicious lesions.
Category: Cytopathology

Wednesday, March 21, 2012 1:00 PM

Poster Session VI # 62, Wednesday Afternoon

 

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