UNESP, São Paulo State University, Department of Biology, Campus São José do Rio Preto, SP, Brazil.
BMC Gastroenterol. 2010 Feb 17;10:20. doi: 10.1186/1471-230X-10-20.
Chagas' disease is a human tropical parasitic illness and a subset of the chronic patients develop megaesophagus or megacolon. The esophagus dilation is known as chagasic megaesophagus (CM) and one of the severe late consequences of CM is the increased risk for esophageal carcinoma (ESCC). Based on the association between CM and ESCC, we investigated whether genes frequently showing unbalanced copy numbers in ESCC were altered in CM by fluorescence in situ (FISH) technology.
A total of 50 formalin-fixed, paraffin-embedded esophageal mucosa specimens (40 from Chagas megaesophagus-CM, and 10 normal esophageal mucosa-NM) were analyzed. DNA FISH probes were tested for FHIT, TP63, PIK3CA, EGFR, FGFR1, MYC, CDKN2A, YES1 and NCOA3 genes, and centromeric sequences from chromosomes 3, 7 and 9.
No differences between superficial and basal layers of the epithelial mucosa were found, except for loss of copy number of EGFR in the esophageal basal layer of CM group. Mean copy number of CDKN2A and CEP9 and frequency of nuclei with loss of PIK3CA were significantly different in the CM group compared with normal mucosa and marginal levels of deletions in TP63, FHIT, PIK3CA, EGFR, CDKN2A, YES and gains at PIK3CA, TP63, FGFR1, MYC, CDNK2A and NCOA3 were detected in few CM cases, mainly with dilation grades III and IV. All changes occurred at very low levels.
Genomic imbalances common in esophageal carcinomas are not present in chagasic megaesophagus suggesting that these features will not be effective markers for risk assessment of ESCC in patients with chagasic megaesophagus.
恰加斯病是一种人类热带寄生虫病，一部分慢性患者会发展为巨食道或巨结肠。食道扩张称为恰加斯巨食道（CM），CM 的严重晚期后果之一是增加患食道癌（ESCC）的风险。基于 CM 与 ESCC 之间的关联，我们通过荧光原位杂交（FISH）技术研究了 CM 中经常出现不平衡拷贝数的基因是否发生改变。
共分析了 50 例福尔马林固定、石蜡包埋的食管黏膜标本（40 例来自恰加斯巨食道-CM，10 例正常食管黏膜-NM）。测试了 FHIT、TP63、PIK3CA、EGFR、FGFR1、MYC、CDKN2A、YES1 和 NCOA3 基因以及染色体 3、7 和 9 的着丝粒序列的 DNA FISH 探针。
除 CM 组食管基底层 EGFR 拷贝数丢失外，上皮黏膜的浅层和深层之间未发现差异。与正常黏膜和边缘缺失水平相比，CM 组 CDKN2A 和 CEP9 的平均拷贝数和 PIK3CA 缺失核的频率明显不同，TP63、FHIT、PIK3CA、EGFR、CDKN2A、YES 和 PIK3CA、TP63、FGFR1、MYC、CDNK2A 和 NCOA3 的增益在少数 CM 病例中检测到，主要与扩张等级 III 和 IV 相关。所有变化都发生在非常低的水平。
在恰加斯巨食道中未发现常见于食道癌的基因组失衡，这表明这些特征不会成为恰加斯巨食道患者 ESCC 风险评估的有效标志物。
