van Weeghel Christiaan, Wierenga Annemijn P A, Versluis Mieke, van Hall Thorbald, van der Velden Pieter A, Kroes Wilma G M, Pfeffer Ulrich, Luyten Gregorius P M, Jager Martine J
Department of Ophthalmology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Department of Clinical Oncology, LUMC, 2333 ZA Leiden, The Netherlands.
Cancers (Basel). 2019 Aug 7;11(8):1127. doi: 10.3390/cancers11081127.
Inflammation, characterized by high numbers of infiltrating leukocytes and a high HLA Class I expression, is associated with a bad prognosis in uveal melanoma (UM). We wondered whether mutations in or differentially affect inflammation and HLA expression, and thereby progression of the disease. We analyzed data of 59 primarily enucleated UM eyes. The type of / mutation was analyzed using dPCR; chromosome aberrations were determined by Fluorescence in Situ Hybridization (FISH), karyotyping, and single nucleotide polymorphism (SNP) analysis, and mRNA expression by Illumina PCR. Comparing tumors with a mutation with those with a mutation yielded no significant differences in histopathological characteristics, infiltrate, or HLA expression. When comparing the Q209L mutations with Q209P mutations in tumors with monosomy of chromosome 3, a higher mitotic count was found in the Q209P/M3 tumors ( = 0.007). The Kaplan-Meier (KM) curves between the patients of the different groups were not significantly different. We conclude that the type (Q209P/Q209L) or location of the mutation (/) do not have a significant effect on the immunological characteristics of the tumors, such as infiltrate and HLA Class I expression. Chromosome 3 status was the main determinant in explaining the difference in infiltrate and HLA expression.
炎症以大量浸润白细胞和高HLA I类表达为特征,与葡萄膜黑色素瘤(UM)的不良预后相关。我们想知道 或 的突变是否会差异影响炎症和HLA表达,进而影响疾病进展。我们分析了59只主要通过眼球摘除获得的UM眼的数据。使用数字PCR分析 / 突变的类型;通过荧光原位杂交(FISH)、核型分析和单核苷酸多态性(SNP)分析确定染色体畸变,并通过Illumina PCR分析mRNA表达。比较有 突变的肿瘤与有 突变的肿瘤,在组织病理学特征、浸润或HLA表达方面未发现显著差异。在比较3号染色体单体型肿瘤中的Q209L突变与Q209P突变时,发现Q209P/M3肿瘤中的有丝分裂计数更高( = 0.007)。不同组患者之间的Kaplan-Meier(KM)曲线无显著差异。我们得出结论,突变的类型(Q209P/Q209L)或位置(/)对肿瘤的免疫特征,如浸润和HLA I类表达,没有显著影响。3号染色体状态是解释浸润和HLA表达差异的主要决定因素。