Monday, August 17, 2015

BRAF V600E and risk stratification of thyroid microcarcinoma: a multicenter pathological and clinical study - ABSTRACT ONLY

Modern Pathology , (14 August 2015) | doi:10.1038/modpathol.2015.92

Giovanni Tallini, Dario de Biase, Cosimo Durante, Giorgia Acquaviva, Michele Bisceglia, Rocco Bruno, Maria Letizia Bacchi Reggiani, Gian Piero Casadei, Giuseppe Costante, Nadia Cremonini, Livia Lamartina, Domenico Meringolo, Francesco Nardi, Annalisa Pession, Kerry J Rhoden, Giuseppe Ronga, Massimo Torlontano, Antonella Verrienti, Michela Visani and Sebastiano Filetti
Studies from single institutions have analyzed BRAF in papillary microcarcinomas, sometimes with contradictory results. Most of them have provided limited integration of histological and clinical data. To obtain a comprehensive picture of BRAF V600E-mutated microcarcinomas and to evaluate the role of BRAF testing in risk stratification we performed a retrospective multicenter analysis integrating microscopical, pathological, and clinical information. Three hundred and sixty-five samples from 300 patients treated at six medical institutions covering different geographical regions of Italy were analyzed with central review of all cases. BRAF V600E statistical analysis was conducted on 298 microcarcinomas from 264 patients after exclusion of those that did not meet the required criteria. BRAF V600E was identified in 145/298 tumors (49%) including the following subtypes: 35/37 (95%, P<0 .0001="" 72="" and="" cell="" class="mb" span="" tall="">/
114 (64%, P<0 .0001="" 94="" class="mb" classic="" conversely="" span="">/129 follicular variant papillary microcarcinomas (73%, P<0 .0001="" 5="" and="" braf="" by="" cells="" characterized="" class="mb" contours="" departing="" elongated="" from="" infiltrative="" intraglandular="" markedly="" microcarcinomas="" neoplastic="" of="" span="" spread="" strings="" the="" tumor="" type.="" typically="" v600e-mutated="" were="" wild="" with="" within="">mm of the tumor border. Multivariate analysis correlated BRAF V600E with specific microscopic features (nuclear grooves, optically clear nuclei, tall cells within the tumor, and tumor fibrosis), aggressive growth pattern (infiltrative tumor border, extension into extrathyroidal tissues, and intraglandular tumor spread), higher American Thyroid Association recurrence risk group, and non-incidental tumor discovery. The following showed the strongest link to BRAF V600E: tall cell subtype, many neoplastic cells with nuclear grooves or with optically clear nuclei, infiltrative growth, intraglandular tumor spread, and a tumor discovery that was non-incidental. BRAF V600E-mutated microcarcinomas represent a distinct biological subtype. The mutation is associated with conventional clinico-pathological features considered to be adverse prognostic factors for papillary microcarcinoma, for which it could be regarded as a surrogate marker. BRAF analysis may be useful to identify tumors (BRAF wild type) that have negligible clinical risk.

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