Papillary Thyroid Carcinoma With exon 15 BRAF Mutation

Papillary Thyroid Carcinoma With Rare exon 15 BRAF Mutation Has Indolent Behavior: A Single-Institution Experience.: The Journal of Clinical Endocrinology &Metabolism, Early Release.







Liborio Torregrossa1, David Viola2, Elisa Sensi1, Mirella Giordano1, Paolo Piaggi2, Cristina Romei2, Gabriele Materazzi3, Paolo Miccoli3, Rossella Elisei2, and Fulvio Basolo1



Address all correspondence and requests for reprints to: Corresponding author and person to whom reprint requests should be addressed: Fulvio Basolo, MD, PhD,

Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, Unit of Pathological Anatomy, Via Roma 57, 56126 Pisa, Italy

, Phone: +39–050-992892, Fax: +39–050-992481, e-mail: fulvio.basolo@med.unipi.it.

DOI: http://ift.tt/2bO4ZTQ



Abstract

Context:

Approximately 40% of papillary thyroid carcinomas (PTC) harbor the BRAF V600E mutation, which is significantly associated with the advanced clinico-pathological features of PTC at diagnosis, higher recurrence rate and disease-related mortality. BRAF alterations other than V600E are less common in PTC, and their clinical significance remains to be established.

Objective:

The aim of the study was to describe a large cohort of rare exon 15 BRAF alterations (r-BRAF), the clinico-pathological features of PTC harboring these alterations and to clarify their clinical significance.

Methods:

A total of 2,961 PTCs were collected from 2006 to 2013 and screened for exon 15 BRAF alterations.

Results:

Exon 15 BRAF alterations were found in 1,186 of 2,961 PTC cases (40.0%). In particular, we found the BRAF V600E mutation in 95.3% (1,131/1,186) and r-BRAF in 4.7% (55/1,186) of the 1,186 cases. r-BRAF were found in 18 microcarcinomas, 33 follicular variants, 1 classic variant and 1 trabecular/solid variant. The most frequent r-BRAF was BRAF K601E (35/55, 63.6%) followed by BRAF V600_K601delinsE (7/55, 12.7%) and BRAF T599I-V600_R603del (2/55, 3.6%). The remaining 11 alterations were found in one case only. The large majority of these tumors were unifocal (34/55, 61.8%), completely encapsulated (46/55, 83.6%) and intrathyroidal (53/55, 96.4%) with a low prevalence of lymph node metastases (1/55, 1.8%) and a less advanced tumor stage at diagnosis (AJCC stage I/II: 51/55, 92.7%).

Conclusions:

r-BRAF are very uncommon in PTC and are found almost exclusively in PTC with low-risk clinico-pathological features.

Affiliations

1Unit of Surgical Pathology, Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy;

2Endocrine Section, Department of Clinical and Experimental Medicine, WHO Collaborating Center for the Study and Treatment of Thyroid Diseases and Other Endocrine and Metabolic Disorders, University of Pisa, Pisa, Italy;

3Endocrine Surgery Unit, Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy

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