结直肠肿瘤吻合口复发的再发：两例病例的基因分析。
Repeated anastomotic recurrence of colorectal tumors: genetic analysis of two cases.
机构信息
Dipartimento di Scienze Chirurgiche, Università degli Studi di Parma, 43100 Parma, Italy.
出版信息
World J Gastroenterol. 2011 Aug 28;17(32):3752-8. doi: 10.3748/wjg.v17.i32.3752.
AIM
To investigate genetics of two cases of colorectal tumor local recurrence and throw some light on the etiopathogenesis of anastomotic recurrence.
METHODS
Two cases are presented: a 65-year-old female receiving two colonic resections for primary anastomotic recurrences within 21 mo, and a 57-year-old female undergoing two local excisions of recurrent anastomotic adenomas within 26 mo. A loss of heterozygosity (LOH) study of 25 microsatellite markers and a mutational analysis of genes BRAF, K-RAS and APC were performed in samples of neoplastic and normal colonic mucosa collected over the years.
RESULTS
A diffuse genetic instability was present in all samples, including neoplastic and normal colonic mucosa. Two different patterns of genetic alterations (LOH at 5q21 and 18p11.23 in the first case, and LOH at 1p34 and 3p14 in the second) were found to be associated with carcinogenesis over the years. A role for the genes MYC-L (mapping at 1p34) and FIHT (mapping at 3p14.2) is suggested, whereas a role for APC (mapping at 5q21) is not shown.
CONCLUSION
The study challenges the most credited intraluminal implantation and metachronous carcinogenesis theories, and suggests a persistent, patient-specific alteration as the trigger of colorectal cancer anastomotic recurrence.
目的
研究两例结直肠肿瘤局部复发的遗传学特征，为吻合口复发的病因学提供一些线索。
方法
报道两例病例：一名 65 岁女性，在 21 个月内接受了两次结肠切除术以治疗原发性吻合口复发；另一名 57 岁女性在 26 个月内两次接受局部切除复发性吻合口腺瘤。对肿瘤和正常结肠黏膜样本进行了 25 个微卫星标记的杂合性丢失（LOH）研究和 BRAF、K-RAS 和 APC 基因的突变分析。
结果
所有样本均存在弥漫性遗传不稳定性，包括肿瘤和正常结肠黏膜。发现两种不同的遗传改变模式（第一例中 5q21 和 18p11.23 的 LOH，第二例中 1p34 和 3p14 的 LOH）与多年来的癌变有关。提示 MYC-L（定位在 1p34）和 FIHT（定位在 3p14.2）基因可能发挥作用，而 APC（定位在 5q21）基因可能没有作用。
结论
该研究对最受认可的腔内植入和异时性癌变理论提出了挑战，提示持续存在的、具有患者特异性的改变可能是结直肠肿瘤吻合口复发的触发因素。
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