Department of Biomedical Sciences, Humanitas University, Milan, Italy.
Humanitas Clinical and Research Center, IRCCS, Milan, Italy.
Thorac Cancer. 2021 May;12(9):1271-1278. doi: 10.1111/1759-7714.13765. Epub 2021 Mar 11.
Significant efforts have been made to investigate the molecular pathways involved in thymic carcinogenesis. However, genetic findings have still not impacted clinical practice. The aim of this exploratory trial was to evaluate the immunoscore and molecular profile of a series of thymic carcinomas (TCs), correlating this data with clinical outcome.
Formalin-fixed, paraffin-embedded (FFPE) TC tissues were retrieved from our center archive. The immunoscore was evaluated according to Angell and Gallon. DNA was extracted from FFPE tumor samples and, when available, from adjacent histologically normal tissues. Next-generation sequencing (NGS) was performed targeting hotspot regions of 50 oncogenes and tumor suppressor genes.
A series of 15 TCs were analyzed. After a median follow-up of 82.4 months, the median overall survival was 104.7 months. The immunoscore was >2 in 5/15 patients (33%). Among the investigated genes, absence of mutations was observed in 5/15 patients (33%), whereas three variants in 1/15 (6%) patient, two variants in 4/15 (26%) patients, and one variant in 5/15 patients (33%) were found. The most recurrently mutated genes were FGFR3 (five mutations) and CDKN2A (three mutations, two of which were nonsense). Patients with CDKN2A loss showed a statistically significantly worse survival (P = 0.0013), whereas patients with FGFR3 mutations showed a statistically significantly better survival (P = 0.048).
This study adds data to the few existing reports on the mutational landscape of TCs, providing the first comprehensive analysis to date. Here, we confirm the low rate of mutations in TCs and suggest FGFR3 and CDKN2A mutations as intriguing potential therapeutic targets.
人们已经做出了巨大努力来研究参与胸腺癌发生的分子途径。然而，遗传发现仍未对临床实践产生影响。本探索性试验的目的是评估一系列胸腺癌 (TC) 的免疫评分和分子特征，并将这些数据与临床结果相关联。
从我们中心的档案中检索到福尔马林固定、石蜡包埋 (FFPE) 的 TC 组织。根据 Angell 和 Gallon 评估免疫评分。从 FFPE 肿瘤样本中提取 DNA，并且在有条件的情况下，从相邻的组织学正常组织中提取 DNA。针对 50 个癌基因和肿瘤抑制基因的热点区域进行下一代测序 (NGS)。
分析了一系列 15 例 TC。中位随访 82.4 个月后，中位总生存期为 104.7 个月。5/15 例患者（33%）的免疫评分>2。在所研究的基因中，15 例患者中有 5 例（33%）未发现突变，1 例（6%）患者有 3 个变异，4 例（26%）患者有 2 个变异，5 例（33%）患者有 1 个变异。最常发生突变的基因是 FGFR3（五个突变）和 CDKN2A（三个突变，其中两个为无义突变）。CDKN2A 缺失的患者生存明显较差（P=0.0013），而 FGFR3 突变的患者生存明显较好（P=0.048）。
本研究为 TC 的突变景观增加了现有少数报告的数据，提供了迄今为止最全面的分析。在这里，我们证实了 TC 中突变的发生率较低，并提示 FGFR3 和 CDKN2A 突变是有前途的潜在治疗靶点。
