Department of General, Visceral, Cancer, and Transplantation Surgery, University of Cologne, Faculty of Medicine, and University Hospital Cologne, Kerpener Straße 62, 50937, Cologne, Germany.
Gastrointestinal Cancer Group Cologne (GCGC), Cologne, Germany.
J Cancer Res Clin Oncol. 2021 Apr;147(4):1031-1040. doi: 10.1007/s00432-020-03486-2. Epub 2020 Dec 10.
Driver mutations are typically absent in esophageal adenocarcinoma (EAC). Mostly, oncogenes are amplified as driving molecular events (including GATA6-amplification in 14% of cases). However, only little is known about its biological function and clinical relevance.
We examined a large number of EAC (n = 496) for their GATA6 amplification by fluorescence in situ hybridization (FISH) analyzing both primary resected (n = 219) and neoadjuvant treated EAC (n = 277). Results were correlated to clinicopathological data and known mutations/amplifications in our EAC-cohort.
GATA6 amplification was detectable in 49 (9.9%) EACs of our cohort. We observed an enrichment of GATA6-positive tumors among patients after neoadjuvant treatment (12,3% amplified tumors versus 6,8% in the primary resected group; p = 0.044). Additionally, there was a simultaneous amplification of PIK3CA and GATA6 (p < 0.001) not detectable when analyzing other genes such as EGFR, ERBB2, KRAS or MDM2. Although we did not identify a survival difference depending on GATA6 in the entire cohort (p = 0.212), GATA6 amplification was associated with prolonged overall survival among patients with primary surgery (median overall-survival 121.1 vs. 41.4 months, p = 0.032). Multivariate cox-regression analysis did not confirm GATA6 as an independent prognostic marker, neither in the entire cohort (p = 0.210), nor in the subgroup with (p = 0.655) or without pretreatment (p = 0.961).
Our study investigates the relevance of GATA6 amplification on a large tumor collective, which includes primary resected tumors and the clinically relevant group of neoadjuvant treated EACs. Especially in the pretreated group, we found an accumulation of GATA6-amplified tumors (12.3%) and a frequent co-amplification of PIK3CA. Our data suggest an increased resistance to radio-chemotherapy in GATA6-amplified tumors.
食管腺癌（EAC）中通常不存在驱动基因突变。大多数情况下，癌基因被扩增作为驱动分子事件（包括 14%的病例中 GATA6 扩增）。然而，人们对其生物学功能和临床相关性知之甚少。
我们通过荧光原位杂交（FISH）分析了大量 EAC（n=496）的 GATA6 扩增情况，包括原发性切除的 EAC（n=219）和新辅助治疗的 EAC（n=277）。结果与我们的 EAC 队列中的临床病理数据和已知的突变/扩增相关联。
我们的队列中 49 例（9.9%）EAC 中可检测到 GATA6 扩增。我们观察到新辅助治疗后 GATA6 阳性肿瘤的富集（扩增肿瘤 12.3%，原发性切除组 6.8%；p=0.044）。此外，同时存在 PIK3CA 和 GATA6 的扩增（p<0.001），而在分析其他基因（如 EGFR、ERBB2、KRAS 或 MDM2）时则无法检测到。尽管我们没有发现整个队列中 GATA6 对生存的影响（p=0.212），但 GATA6 扩增与原发性手术患者的总生存期延长相关（中位总生存期 121.1 与 41.4 个月，p=0.032）。多变量 Cox 回归分析并未确认 GATA6 是独立的预后标志物，无论是在整个队列中（p=0.210），还是在预处理亚组（p=0.655）或无预处理亚组（p=0.961）中均未确认。
我们的研究在一个包括原发性切除肿瘤和临床相关新辅助治疗 EAC 组的大型肿瘤队列中研究了 GATA6 扩增的相关性。特别是在预处理组中，我们发现 GATA6 扩增肿瘤（12.3%）的积累和 PIK3CA 的频繁共扩增。我们的数据表明，GATA6 扩增的肿瘤对放化疗的抵抗力增加。
