Analysis of immunocytochemical and molecular BRAF expression in thyroid carcinomas: A cytohistologic institutional experience. Issue 7 (17th March 2014)

• Record Type: Journal Article
• Authors: Rossi, Esther Diana; Martini, Maurizio; Capodimonti, Sara; Cenci, Tonia; Straccia, Patrizia; Angrisani, Basilio; Ricci, Costantino; Lanza, Paola; Lombardi, Celestino Pio; Pontecorvi, Alfredo; Larocca, Luigi Maria; Fadda, Guido
• Is Part Of: Cancer cytopathology. Volume 122:Issue 7(2014:Jul.)
• Page Start: 527
• Page End: 535
• Publication Date: 2014-03-17
• Subjects: thyroid papillary carcinoma -- liquid‐based cytology -- BRAF mutation -- immunochemistry -- VE1 immunomarker; Cancer -- Cytopathology -- Periodicals; Pathology, Cellular -- Periodicals; Cytology -- Technique -- Periodicals; 611.01815
• DOI: 10.1002/cncy.21416
• Languages: English
• ISSNs: 1934-662X

Abstract

Abstract : BACKGROUND: It has been generally demonstrated that the valine‐to‐glutamic acid substitution at position 600 (V600E) in the v‐Raf murine sarcoma viral oncogene homolog B1 ( BRAF ) gene is an effective diagnostic/prognostic marker mainly for papillary thyroid carcinoma (PTC). The detection of this mutation typically has been achieved using DNA‐based techniques. The recently introduced monoclonal V600E antibody (clone VE1) is likely to be an alternative strategy for detecting this mutation in thyroid lesions. The authors investigated molecular and immunocytohistochemical BRAF analyses in a prospective series of samples from patients with PTC. METHODS: Fifty‐five prospective cytohistologic samples that were diagnosed as PTC were studied using both DNA BRAF testing and the VE1 antibody. The intensity of VE1 expression was graded from 0 (negative) to 3+ (strong). RESULTS: All diagnoses were histologically confirmed. In total, 37 samples with mutated BRAF and 18 samples with wild‐type BRAF were reported with 100% cytohistologic concordance. Cytologic VE1 expression revealed 25 negative samples (including 16 with 0 expression and 9 with 1+ expression) and 30 positive samples (including 16 with 2+ expression and 14 with 3+ expression). On histology, there were 27 negative samples (20 with 0 expression and 7 with 1+ expression) and 28 positive samples (14 with 2+ expression and 14 with 3+ expression). Four specimens with the BRAF mutation had discrepancies in VE1 intensity between cytology and histology. Furthermore, 6 BRAF ‐mutated samples produced negative VE1 results. CONCLUSIONS: Although it has limitations, the VE1 antibody represents a feasible first‐line approach for evaluating BRAF mutation status and may be a valid tool in the selection of samples for molecular analysis. The current report highlights the statistically significant difference between molecular and VE1 positivity in PTC ( P < .0001). Nevertheless, in the authors' experience, BRAF mutations are more accurate for identifying VE1‐negative cases. Cancer (Cancer Cytopathol) 2014;122:527–535 . © 2014 American Cancer Society . Abstract : BRAF mutation is a strong indicator of papillary thyroid cancer because of its high specificity and positive predictive value, and it can easily be evaluated on thyroid cytologic samples. The new VE1 immunomarker—a monoclonal antibody directed against the mutated BRAF V600E protein—may be a valid alternative to DNA‐based methods and produces good results in the presence of moderate and/or strong expression.