在结肠镜筛查期间,只有肉眼可见的病变才能被识别,这些通常是多重遗传异常的结果。放大内镜检测异常隐窝病灶(ACF),在他们获得复杂的遗传异常之前很久,很有希望。然而,需要识别高危ACF样病变的特征.
在本横断面研究中,从152个结肠切除术中刮去了明显可见的正常粘膜瓣,包括96例结直肠癌(CRC)病例和56例对照(22例具有恶性潜能的对照标本和34例无恶性潜能的对照标本)。直接在未固定的粘膜瓣上进行亚甲基和阿尔辛蓝染色,以鉴定ACF和粘蛋白耗尽的病灶(MDF)。详细的地形分析,对β-catenin和肿瘤干细胞(CSC)标志物(CD44,CD24和CD166)进行免疫组织化学染色.
ACF,MDF,在具有相邻CRC的标本中检测到更多的β-catenin积累的隐窝。左结肠有一个更大的直径和更大的隐窝多重性的ACF,密度,和回旋坑模式,被认为是高危ACF组。MDF,更常见的与发育不良有关,也是可能致癌的标志。与正常对照相比,ACF标本中的CD44CSC标记物显着上调。与6层Kudo分类相比,我们的3层ACF仅凹坑模式分类系统与粘膜发育不良的线性更好。
高风险ACF,当在染色体内镜筛查中检测到时,应该跟进。CSCs可能在发病机制中起重要作用。需要进行更大规模的研究和基因型风险分层,以明确识别高风险ACF。
During colonoscopic screening, only macroscopic lesions will be identified, and these are usually the result of multiple genetic abnormalities. Magnification endoscopic detection of aberrant crypt foci (ACF), long before they acquire complex genetic abnormalities, is promising. However, the features of high-risk ACF-like lesions need to be identified.
In the present cross-sectional
study, grossly visible normal mucosal flaps were shaved from 152 colectomies, including 96 colorectal cancer (CRC) cases and 56 controls (22 control specimens with disease with malignant potential and 34 without malignant potential). Methylene and Alcian blue stains were performed directly on the unfixed mucosal flaps to identify ACF and mucin-depleted foci (MDF). Detailed topographic analyses, with immunohistochemical staining for β-catenin and cancer stem cell (CSC) markers (CD44, CD24, and CD166) were performed.
ACF, MDF, and β-catenin-accumulated crypts were detected more in specimens with adjacent CRC. The left colon had ACF with a larger diameter and greater crypt multiplicity, density, and gyriform pit pattern and were considered the high-risk ACF group. MDF, more commonly associated with dysplasia, is also a marker of possible carcinogenesis. The CD44 CSC marker was significantly upregulated in ACF specimens compared with normal controls. Our 3-tier ACF-only pit pattern classification system showed better linearity with mucosal dysplasia than did the 6-tier Kudo classification.
High-risk ACF, when detected during chromoendoscopic screening, should be followed up. CSCs might play an important role in pathogenesis. Larger studies and genotypic risk stratification for definite identification of high-risk ACF are needed.