1] Department of Pathology, Friedrich-Alexander Universität Erlangen-Nürnberg, Krankenhausstrasse 8/10, 91054 Erlangen, Germany [2] Comprehensive Cancer Center Erlangen-European Metropolitan Region Nuremberg 91054 Erlangen, Germany.
Department of Pathology, University Hospital Regensburg, 93053 Regensburg, Germany.
Br J Cancer. 2014 Jun 10;110(12):2985-95. doi: 10.1038/bjc.2014.238. Epub 2014 May 22.
Oesophageal adenocarcinoma or Barrett's adenocarcinoma (EAC) is increasing in incidence and stratification of prognosis might improve disease management. Multi-colour fluorescence in situ hybridisation (FISH) investigating ERBB2, MYC, CDKN2A and ZNF217 has recently shown promising results for the diagnosis of dysplasia and cancer using cytological samples.
To identify markers of prognosis we targeted four selected gene loci using multi-colour FISH applied to a tissue microarray containing 130 EAC samples. Prognostic predictors (P1, P2, P3) based on genomic copy numbers of the four loci were statistically assessed to stratify patients according to overall survival in combination with clinical data.
The best stratification into favourable and unfavourable prognoses was shown by P1, percentage of cells with less than two ZNF217 signals; P2, percentage of cells with fewer ERBB2- than ZNF217 signals; and P3, overall ratio of ERBB2-/ZNF217 signals. Median survival times for P1 were 32 vs 73 months, 28 vs 73 months for P2; and 27 vs 65 months for P3. Regarding each tumour grade P2 subdivided patients into distinct prognostic groups independently within each grade, with different median survival times of at least 35 months.
Cell signal number of the ERBB2 and ZNF217 loci showed independence from tumour stage and differentiation grade. The prognostic value of multi-colour FISH-assays is applicable to EAC and is superior to single markers.
食管腺癌或 Barrett 腺癌（EAC）的发病率正在增加，对其进行分层以改善预后可能有助于疾病的管理。多色荧光原位杂交（FISH）检测 ERBB2、MYC、CDKN2A 和 ZNF217 最近已显示出在使用细胞学样本诊断异型增生和癌症方面的良好结果。
为了确定预后标志物，我们使用多色 FISH 针对包含 130 个 EAC 样本的组织微阵列中的四个选定基因座进行靶向检测。基于四个基因座的基因组拷贝数，通过统计学方法评估预后预测因子（P1、P2、P3），以根据总体生存率并结合临床数据对患者进行分层。
P1（ZNF217 信号少于两个的细胞百分比）、P2（ERBB2 信号少于 ZNF217 信号的细胞百分比）和 P3（ERBB2/ZNF217 信号的总体比值）的最佳分层显示出有利和不利的预后。P1 的中位生存时间为 32 个月对比 73 个月，P2 为 28 个月对比 73 个月，P3 为 27 个月对比 65 个月。对于每个肿瘤分级，P2 独立于肿瘤分级和分化程度将患者分为不同的预后组，至少有 35 个月的不同中位生存时间。
ERBB2 和 ZNF217 基因座的细胞信号数量独立于肿瘤分期和分化程度。多色 FISH 检测的预后价值适用于 EAC，优于单标记物。
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