Otori K, Sugiyama K, Hasebe T, Fukushima S, Esumi H
Investigative Treatment Division, National Cancer Center Research Institute, Chiba, Japan.
Cancer Res. 1995 Nov 1;55(21):4743-6.
To investigate the relationship between aberrant crypt foci (ACF) and colon neoplasia in colorectal carcinogenesis, we evaluated 433 ACF, which were collected from the grossly normal mucosa of surgical specimens from 57 patients with colorectal cancer. The ACF ranged in size from 3 to 412 aberrant crypts/focus. Large ACF (> or = 50 crypts/focus) comprised 25% of the total ACF studied. Histopathologically, 65% (67 of 103) of large ACF were diagnosed as hyperplasia, 10% (10 of 103) as adenoma, and 1% (1 of 103) as within normal colorectal mucosa. The remaining 24% (25 of 103) were diagnosed as "stage I abnormality crypts," which were characterized by their extension of the proliferative compartment to the surface of crypts but with no changes in the major site of proliferation, as designated by E. E. Deschner [Pathol. Annu., 18 (Part 1): 205-219, 1983]. Of the 25 stage I abnormality ACF, 7 ACF coexisted with hyperplasia. Of 10 adenomatous ACF, two coexisted with stage I abnormality crypts. A K-ras codon 12 mutation was identified in 85% (93 of 109) of large ACF. The proliferative activity of stage I crypts was significantly higher than that of hyperplastic crypts in the same ACF. These observations suggest that some hyperplastic ACF may develop into adenomatous ACF by way of stage I abnormality ACF with concomitant acquisition of higher proliferative activity through some genetic and/or epigenetic changes.
为了研究大肠癌变过程中异常隐窝灶（ACF）与结肠肿瘤形成之间的关系，我们评估了433个ACF，这些ACF取自57例结肠癌患者手术标本的大体正常黏膜。ACF的大小范围为每个病灶有3至412个异常隐窝。大的ACF（≥50个隐窝/病灶）占所研究ACF总数的25%。组织病理学检查显示，65%（103个中的67个）的大ACF被诊断为增生，10%（103个中的10个）为腺瘤，1%（103个中的1个）为正常大肠黏膜。其余24%（103个中的25个）被诊断为“Ⅰ期异常隐窝”，其特征是增殖区延伸至隐窝表面，但主要增殖部位无变化，这是由E.E. Deschner所定义的[《病理学年度报告》，18（第1部分）：205 - 219，1983]。在25个Ⅰ期异常ACF中，有7个ACF与增生共存。在10个腺瘤性ACF中，有2个与Ⅰ期异常隐窝共存。在85%（109个中的93个）的大ACF中检测到K-ras密码子12突变。同一ACF中Ⅰ期隐窝的增殖活性明显高于增生性隐窝。这些观察结果表明，一些增生性ACF可能通过Ⅰ期异常ACF发展为腺瘤性ACF，同时通过一些基因和/或表观遗传变化获得更高的增殖活性。
