Rygiel Agnieszka M, Milano Francesca, Ten Kate Fibo J, Schaap Annet, Wang Kenneth K, Peppelenbosch Mackel P, Bergman Jacques J G H M, Krishnadath Kausillia K
Laboratory of Experimental Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands.
Cancer Epidemiol Biomarkers Prev. 2008 Jun;17(6):1380-5. doi: 10.1158/1055-9965.EPI-07-2734.
The progression of Barrett's esophagus to esophageal adenocarcinoma is often characterized by the accumulation of genetic abnormalities. The goal was to evaluate the copy number alterations of several oncogene loci, including 7p12 [epidermal growth factor receptor (EGFR)], 8q24 (c-myc), and 20q13 in the sequence of no dysplasia-dysplasia-adenocarcinoma of Barrett's esophagus. Fluorescence in situ hybridization with DNA probes for the centromeric region of chromosome 7 and the locus-specific regions of 7p12 (EGFR), 8q24 (c-myc), and 20q13 was applied on 99 brush cytology specimens of patients with Barrett's esophagus with different stages of dysplasia or esophageal adenocarcinoma. Gains (3-4 copies) of chromosome 17, 8q24 (c-myc), and 20q.13 loci were found in the low frequencies in nondysplastic Barrett's esophagus. Their frequencies increased with the stage of dysplasia and reached a high incidence in esophageal adenocarcinoma. Amplification (>4 copies) of at least 1 of the loci was observed in 14% of high-grade dysplasia and increased to 50% in esophageal adenocarcinoma (P = 0.015). The most frequently amplified locus was c-myc (18%), followed by 20q13 (13%) and EGFR (11%) in the high-grade dysplasia/esophageal adenocarcinoma cases. High amplification levels (>10 copies) of the loci were more frequent in esophageal adenocarcinoma (72%) compared with high-grade dysplasia (20%; P = 0.049). Amplifications of the c-myc, EGFR, and 20q12 loci may serve as diagnostic markers to identify patients with Barrett's esophagus with high-grade dysplasia or esophageal adenocarcinoma. Gains of the loci might be of value as prognostic markers because they are already present in nondysplasia cases and may precede the later event of the amplification as observed in high-grade dysplasia and esophageal adenocarcinoma.
巴雷特食管进展为食管腺癌通常以基因异常的积累为特征。目的是评估几个癌基因位点的拷贝数改变，包括7p12[表皮生长因子受体(EGFR)]、8q24(c-myc)和20q13在巴雷特食管无发育异常-发育异常-腺癌序列中的情况。应用针对7号染色体着丝粒区域以及7p12(EGFR)、8q24(c-myc)和20q13位点特异性区域的DNA探针进行荧光原位杂交，对99例不同发育异常阶段或食管腺癌的巴雷特食管患者的刷检细胞学标本进行检测。在无发育异常的巴雷特食管中，17号染色体、8q24(c-myc)和20q.13位点的增益(3 - 4个拷贝)出现频率较低。它们的频率随着发育异常阶段的增加而升高，在食管腺癌中达到高发病率。在14%的高级别发育异常中观察到至少1个位点的扩增(>4个拷贝)，在食管腺癌中增至50%(P = 0.015)。在高级别发育异常/食管腺癌病例中，最常扩增的位点是c-myc(18%)，其次是20q13(13%)和EGFR(11%)。与高级别发育异常(20%;P = 0.049)相比，这些位点的高扩增水平(>10个拷贝)在食管腺癌中更常见(72%)。c-myc、EGFR和20q12位点的扩增可能作为诊断标志物，用于识别患有高级别发育异常或食管腺癌的巴雷特食管患者。这些位点的增益可能作为预后标志物具有价值，因为它们在无发育异常的病例中已经存在，并且可能在高级别发育异常和食管腺癌中观察到的扩增这一后期事件之前出现。
