Endocrine Abstracts

Background: Papillary thyroid carcinoma (PTC), especially its classic papillary, oncocytic, Warthin-like, tall and columnar cell variants, is characterized by a high frequency of BRAFV600E mutation that varies in different studies from 36 to 85%. Prognostic significance of the mutation remains controversial.

Objective: Aim of the study was an analysis of relationship between clinical, morphological and prognostic characteristics of PTC with BRAFV600E assessed immunohistochemically.

Material and methods: Histological and immunohistochemical study of formalin-fixed paraffin-embedded sections of primary, metastatic and recurrent (if available) PTC was conducted with mouse monoclonal antibodies to protein products of mutated BRAF in 74 patients (18 males and 56 females aged from 9 to 80 years. at the time of first operation). Results of immunohistochemistry were scored by three pathologists, and agreed opinion was considered for analysis of relationship between BRAF mutational status and clinical, morphological and prognostic features of PTC.

Results: Mutant BRAF status was observed in 29 of 74 PTC (39%). BRAF positive group of PTC was characterized by higher proportion of male patients (37.9 vs 15.5%, P=0.050), older age at the time of operation (39.3 vs 28.4 years., P=0.005), and higher frequency of advanced clinical stages (37.9 vs 13.3%, P=0.023). Classic papillary histotype of PTC was diagnosed more often (65.5 vs 35.5%, P=0.017), and frequency of tumor post-operational relapses was higher (62.1 vs 33.3%, P=0.018) in BRAF positive group in comparison with BRAF negative. BRAF negative group displayed a higher frequency of distant metastases, the volume of surgical operation was generally larger. No significant difference with regard to BRAF status was found for pT, pN categories, extrathyroidal tumor extension, multifocality, and encapsulation. Analysis of disease-free survival based on multivariate proportional hazard models demonstrated significantly elevated rate of relapse in the BRAF positive group, and that BRAF mutation was a prognostic factor of time-related tumor relapse independent from the extent of surgery.

Conclusions: The BRAF mutation is an important risk factor for PTC relapse that may be useful for prognostication during post-operational follow up.