Zurnadzhy Liudmyla, Bogdanova Tetiana, Rogounovitch Tatiana I, Ito Masahiro, Tronko Mykola, Yamashita Shunichi, Mitsutake Norisato, Chernyshov Serhii, Masiuk Sergii, Saenko Vladimir A
State Institution "V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine", 69 Vyshgorodska Str., 04114 Kyiv, Ukraine.
Department of Radiation Molecular Epidemiology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Cancers (Basel). 2021 Nov 30;13(23):6038. doi: 10.3390/cancers13236038.
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 BRAF-positive PTCs, whose proportion is growing with time, are not well described yet. We analyzed the relationship between the BRAF 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 BRAF was increasing with patient age, consistently remaining lower in radiogenic PTCs. In both etiopathogenic groups, the BRAF-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 BRAF-negative tumors. Comparison of the BRAF-positive PTCs across the groups found a virtual absence of differences. In contrast, the BRAF-negative radiogenic PTCs displayed less frequent dominant papillary and more frequent solid growth patterns, lower Ki67 labeling index, and higher invasiveness than the BRAF-negative sporadic tumors. Thus, BRAF 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 BRAF-negative tumors.
对受切尔诺贝利核事故辐射影响的儿童和青少年的融合致癌基因驱动的甲状腺乳头状癌(PTC)的组织病理学变化已进行了广泛研究。然而,随着时间推移比例不断增加的辐射诱导的BRAF阳性PTC的特征尚未得到充分描述。我们分析了BRAF状态(使用VE1抗体通过免疫组织化学方法确定)与247例辐射诱导的和138例散发性PTC(来自年龄≤28岁的乌克兰年轻患者)的临床病理特征之间的关系。BRAF的频率随患者年龄增加,在辐射诱导的PTC中一直较低。在两个病因组中,BRAF阳性的PTC更常具有优势乳头状生长模式、肿瘤较小、Ki67标记指数较高,且肿瘤侵袭主要指标的频率低于或等于BRAF阴性肿瘤。对两组BRAF阳性PTC的比较发现几乎没有差异。相比之下,BRAF阴性的辐射诱导的PTC与BRAF阴性的散发性肿瘤相比,优势乳头状生长模式较少见,实性生长模式较常见,Ki67标记指数较低,侵袭性较高。因此,无论病因如何,BRAF与年轻患者中PTC更具侵袭性的病程无关。辐射诱导的和散发性PTC之间的主要临床病理差异在BRAF阴性肿瘤中观察到。