Department of Endocrinology and Metabolism and World Health Organization Collaborating Center for the Study and Treatment of Thyroid Diseases and Other Endocrine and Metabolic Disorders, University of Pisa, 56124 Pisa, Italy.
J Clin Endocrinol Metab. 2012 Sep;97(9):E1758-65. doi: 10.1210/jc.2012-1269. Epub 2012 Jun 28.
Evidence for an increased prevalence of BRAF(V600E) mutations has been documented in recent decades. The aim of this study was to evaluate the prevalence of both RET/PTC rearrangements and BRAF(V600E) mutations in an Italian cohort of papillary thyroid carcinoma (PTC) patients followed at the Endocrine Units of Pisa, Milano, and Perugia from 1996-2010.
In total, 401 PTC patients were examined and grouped according to the time of surgery: group 1, 1996-2000; group 2, 2001-2005; and group 3, 2006-2010. Patients were analyzed for clinical, pathological, and molecular features. In parallel, the molecular characteristics of 459 PTC from Sicily were studied.
The genetic profiles of the three groups were significantly different (P < 0.0001). In particular, the frequency of RET/PTC rearrangements decreased from 1996-2010, occurring in 33 of 100 (33%) of the patients in group 1, 26 of 148 (17%) in group 2, and 15 of 153 (9.8%) in group 3. The incidence of BRAF(V600E) mutations increased over the same period, from 28% in group 1 (28 of 100) to 48.9% in group 2 (73 of 148) and 58.1% in group 3 (89 of 153). A consistent increase in BRAF(V600E) prevalence was observed in the Sicilian group (P < 0.0001). Moreover, a statistically significant increase in the mean age at diagnosis and decrease in tumor size over the study period was observed.
The genetic profile of PTC changed over the last 15 yr, with a significant decrease in the prevalence of RET/PTC rearrangements and an increase in BRAF(V600E) mutations. In addition, the mean age at diagnosis increased and tumor size decreased over the study period.
近年来有证据表明 BRAF(V600E) 突变的患病率有所增加。本研究的目的是评估意大利比萨、米兰和佩鲁贾内分泌科在 1996-2010 年间收治的甲状腺乳头状癌 (PTC) 患者的 RET/PTC 重排和 BRAF(V600E) 突变的患病率。
共检查了 401 例 PTC 患者，并根据手术时间进行分组：第 1 组为 1996-2000 年；第 2 组为 2001-2005 年；第 3 组为 2006-2010 年。分析了患者的临床、病理和分子特征。同时，还研究了来自西西里岛的 459 例 PTC 的分子特征。
三组的遗传特征差异显著 (P < 0.0001)。特别是，RET/PTC 重排的频率从 1996-2010 年逐渐降低，第 1 组 100 例患者中有 33 例 (33%)、第 2 组 148 例患者中有 26 例 (17%)、第 3 组 153 例患者中有 15 例 (9.8%)发生。同期 BRAF(V600E) 突变的发生率增加，第 1 组 100 例患者中有 28 例 (28%)、第 2 组 148 例患者中有 73 例 (48.9%)、第 3 组 153 例患者中有 89 例 (58.1%)发生。西西里组的 BRAF(V600E) 患病率也呈持续增加趋势 (P < 0.0001)。此外，研究期间还观察到诊断时的平均年龄和肿瘤大小呈统计学显著增加。
过去 15 年，PTC 的基因谱发生了变化，RET/PTC 重排的发生率显著降低，BRAF(V600E) 突变的发生率增加。此外，研究期间诊断时的平均年龄增加，肿瘤大小减小。
