De Filippo C, Luceri C, Caderni G, Pacini M, Messerini L, Biggeri A, Mini E, Tonelli F, Cianchi F, Dolara P
Dept of Pharmacology, University of Florence, Italy.
Scand J Gastroenterol. 2002 Sep;37(9):1048-53. doi: 10.1080/003655202320378248.
Mutations of the APC gene are reported to occur frequently in sporadic colorectal adenomas and adenocarcinomas. We studied APC gene mutations in cases of human sporadic colorectal cancer in order to evaluate their correlation with pathologic characteristics and clinical prognosis.
Most of the mutations of the APC gene (95%) are nonsense or frame shift mutations, encoding for truncated APC proteins. For this reason, mutation detection of the APC gene was performed using the in vitro synthesized protein (IVSP) assay, analysing the region between nucleotide 2058 and nucleotide 5079 of the gene, containing the mutation cluster region.
Out of 58 cases of colorectal cancer, 29 presented a mutated form of APC (mutation frequency 50%). We did not find a statistically significant correlation between APC gene mutation and age, sex, localization of the primary tumour, grading, Crohn-like lymphoid reaction or presence of residual adenoma. Tumours with low invasivity (Dukes' stages A and B) were less frequently mutated (12/27, 44.5%) than tumours of Dukes' stage C (15 out of 21, 71.4%), which developed macroscopically secondary metastasis with variable latency after surgery. Highly invasive tumours with synchronous metastases (Dukes' stage D) had, instead, a low frequency of APC mutations (20%, 2/10) (P = 0.02, compared with Dukes' stages A, B and C).
These data suggest that more aggressive Dukes' stage D tumours develop metastasis by means of an unknown mechanism, independent of APC mutation.
据报道，APC基因的突变在散发性结肠直肠腺瘤和腺癌中频繁发生。我们研究了人类散发性结直肠癌病例中的APC基因突变，以评估它们与病理特征和临床预后的相关性。
APC基因的大多数突变（95%）为无义或移码突变，编码截短的APC蛋白。因此，使用体外合成蛋白（IVSP）分析法检测APC基因的突变，分析该基因2058核苷酸至5079核苷酸之间包含突变簇区域的片段。
在58例结直肠癌病例中，29例呈现APC基因的突变形式（突变频率为50%）。我们未发现APC基因突变与年龄、性别、原发肿瘤部位、分级、克罗恩样淋巴反应或残留腺瘤的存在之间存在统计学上的显著相关性。侵袭性低的肿瘤（Dukes分期A和B）的突变频率（12/27，44.5%）低于Dukes分期C的肿瘤（21例中有15例，71.4%），后者在手术后会在不同潜伏期出现肉眼可见的继发性转移。相反，伴有同步转移的高侵袭性肿瘤（Dukes分期D）的APC基因突变频率较低（20%，2/10）（与Dukes分期A、B和C相比，P = 0.02）。
这些数据表明，侵袭性更强的Dukes分期D肿瘤通过一种未知机制发生转移，与APC基因突变无关。
