The BRAFV600E Mutation Is Not a Risk Factor for More Aggressive Tumor Behavior in Radiogenic and Sporadic Papillary Thyroid Carcinoma at a Young Age

Liudmyla Zurnadzhy,Norisato Mitsutake,Tetiana Bogdanova,Serhii Chernyshov,Mykola Tronko,Sergii Masiuk,Shunichi Yamashita,Masahiro Ito,Vladimir A Saenko,Tatiana I Rogounovitch

doi:10.3390/cancers13236038

Abstract

Simple SummaryAnalysis of the groups of young Ukrainian patients (aged ≤28 years) with radiogenic and sporadic papillary thyroid carcinomas (PTCs) showed that the frequency of BRAFV600E was increasing with patient age, consistently remaining lower in radiogenic PTCs. In both etiopathogenic groups, the BRAFV600E-positive PTCs more frequently had a dominant papillary growth pattern, smaller tumor size, higher Ki67 labeling index, and a frequency of the major indicators of tumor invasiveness that is lower than or equal to that of the BRAFV600E-negative tumors. Comparison of the BRAFV600E-positive PTCs across the groups found a virtual absence of differences, while the BRAFV600E-negative tumors differed markedly and displayed a higher frequency of invasive tumor features in the radiogenic PTCs. Hence, there is evidence that BRAFV600E does not confer a more aggressive course of PTC in young patients regardless of tumor etiology.Histopathological changes in the fusion oncogene-driven papillary thyroid carcinomas (PTCs) from children and adolescents exposed to Chernobyl fallout have been extensively studied. However, characteristics of the radiogenic BRAFV600E-positive PTCs, whose proportion is growing with time, are not well described yet. We analyzed the relationship between the BRAFV600E status (determined immunohistochemically with the VE1 antibody) and the clinicopathological features of 247 radiogenic and 138 sporadic PTCs from young Ukrainian patients aged ≤28 years. The frequency of BRAFV600E was increasing with patient age, consistently remaining lower in radiogenic PTCs. In both etiopathogenic groups, the BRAFV600E-positive PTCs more frequently had a dominant papillary growth pattern, smaller tumor size, higher Ki67 labeling index, and a frequency of the major indicators of tumor invasiveness that is lower than or equal to that of the BRAFV600E-negative tumors. Comparison of the BRAFV600E-positive PTCs across the groups found a virtual absence of differences. In contrast, the BRAFV600E-negative radiogenic PTCs displayed less frequent dominant papillary and more frequent solid growth patterns, lower Ki67 labeling index, and higher invasiveness than the BRAFV600E-negative sporadic tumors. Thus, BRAFV600E is not associated with a more aggressive course of PTC in young patients regardless of etiology. The major clinicopathological differences between the radiogenic and sporadic PTCs are observed among the BRAFV600E-negative tumors.

Highlights

A sharp increase in the incidence of thyroid cancer among subjects aged ≤18 years in 1986 is the major health consequence of the Chernobyl accident in the exposed population.A number of studies addressing epidemiology, molecular characteristics, and clinical and pathological features of radiation-related thyroid cancer have been conducted to date.Clinicopathological and molecular characteristics of the Chernobyl thyroid cancer, principally papillary thyroid carcinoma (PTC), have been shown to evolve with time.Tumors developing after the shorter latency (1st decade after the accident) were frequently more aggressive, especially in children and adolescents; many tumors had a solid growth pattern [1,2,3]
Positive IHC reactions with the antibody to the mutant BRAFV600E protein were detected in the radiogenic series in only one of 104 PTC cases (1.0%) in children, in 6/52 of cases (11.5%) in adolescents, and 19/91 of cases (20.9%) in young adults (Table 1)
Our study demonstrates that the BRAFV600E mutation is more frequent in sporadic than in radiogenic PTCs in all age groups of patients, and that mutational frequency significantly increases with patient age in both radiogenic and sporadic PTCs

Summary

Introduction

A sharp increase in the incidence of thyroid cancer among subjects aged ≤18 years in 1986 is the major health consequence of the Chernobyl accident in the exposed population.A number of studies addressing epidemiology, molecular characteristics, and clinical and pathological features of radiation-related thyroid cancer have been conducted to date.Clinicopathological and molecular characteristics of the Chernobyl thyroid cancer, principally papillary thyroid carcinoma (PTC), have been shown to evolve with time.Tumors developing after the shorter latency (1st decade after the accident) were frequently more aggressive, especially in children and adolescents; many tumors had a solid growth pattern [1,2,3]. A number of studies addressing epidemiology, molecular characteristics, and clinical and pathological features of radiation-related thyroid cancer have been conducted to date. Clinicopathological and molecular characteristics of the Chernobyl thyroid cancer, principally papillary thyroid carcinoma (PTC), have been shown to evolve with time. Tumors developing after the shorter latency (1st decade after the accident) were frequently more aggressive, especially in children and adolescents; many tumors had a solid growth pattern [1,2,3]. PTCs diagnosed in the 2nd or 3rd decades after the accident after the longer period of latency displayed a less aggressive phenotype; the dominant papillary morphology was more common [3]. Radiation-related PTCs in young patients were found to display pathological features of tumor aggressiveness more frequently than

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