Kleist Britta, Meurer Thuja, Poetsch Micaela
1 Department of Pathology, Southern Hospital Trust, Kristiansand, Norway.
2 Institute of Legal Medicine, University Hospital Essen, Essen, Germany.
Tumour Biol. 2017 Mar;39(3):1010428317692246. doi: 10.1177/1010428317692246.
This study attempts to determine whether primary tumor tissue could reliably represent metastatic colorectal cancer in therapy-guiding analysis of mitochondrial microsatellite instability. Therefore, we investigated the concordance of microsatellite instability in D310, D514, and D16184 (mitochondrial DNA displacement loop), and its association with selected clinical categories and KRAS/NRAS/BRAF/PIK3CA/TP53 mutation status between primary and metastatic colorectal cancer tissue from 119 patients. Displacement loop microsatellite instability was significantly more frequently seen in lymph node metastases (53.1%) compared to primary tumors (37.5%) and distant metastases (21.4%) ( p = 0.0183 and p = 0.0005). The discordant rate was significantly higher in lymph node metastases/primary tumor pairs (74.6%) than in distant metastases/primary tumor pairs (52.4%) or lymph node metastases/distant metastases pairs (51.6%) ( p = 0.0113 and p = 0.0261) with more gain (86.7%) than loss (61.1%) of microsatellite instability in the discordant lymph node metastases ( p = 0.0024). Displacement loop instability occurred significantly more frequently in lymph node metastases and distant metastases of patients with early colorectal cancer onset age <60 years ( p = 0.0122 and p = 0.0129), was found with a significant high rate in a small cohort of TP53-mutated distant metastases ( p = 0.0418), and was associated with TP53 wild-type status of primary tumors ( p = 0.0009), but did not correlate with KRAS, NRAS, BRAF, or PIK3CA mutations. In conclusion, mitochondrial microsatellite instability and its association with selected clinical and molecular markers are discordant in primary and metastatic colorectal cancer, which could have importance for surveillance and therapeutic strategies.
本研究旨在确定在指导线粒体微卫星不稳定性治疗分析中，原发性肿瘤组织是否能可靠地代表转移性结直肠癌。因此，我们调查了119例患者原发性和转移性结直肠癌组织中D310、D514和D16184（线粒体DNA位移环）的微卫星不稳定性的一致性，及其与选定临床类别和KRAS/NRAS/BRAF/PIK3CA/TP53突变状态的相关性。与原发性肿瘤（37.5%）和远处转移（21.4%）相比，位移环微卫星不稳定性在淋巴结转移中显著更常见（53.1%）（p = 0.0183和p = 0.0005）。淋巴结转移/原发性肿瘤对中的不一致率（74.6%）显著高于远处转移/原发性肿瘤对（52.4%）或淋巴结转移/远处转移对（51.6%）（p = 0.0113和p = 0.0261），在不一致的淋巴结转移中微卫星不稳定性增加（86.7%）比减少（61.1%）更常见（p = 0.0024）。位移环不稳定性在结直肠癌发病年龄<60岁的患者的淋巴结转移和远处转移中显著更频繁出现（p = 0.0122和p = 0.0129），在一小群TP53突变的远处转移中发现率显著较高（p = 0.0418），并且与原发性肿瘤的TP53野生型状态相关（p = 0.0009），但与KRAS、NRAS、BRAF或PIK3CA突变无关。总之，原发性和转移性结直肠癌中线粒体微卫星不稳定性及其与选定临床和分子标志物的相关性不一致，这可能对监测和治疗策略具有重要意义。
