Newly defined aberrant crypt foci as a marker for dysplasia in the rat colon.

Newly defined aberrant crypt foci as a marker for dysplasia in the rat colon.
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DOI:
10.1111/cas.12446
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发表时间:
2014-08
期刊:
影响因子:
5.7
通讯作者:
Nakagama H
Nakagama H
中科院分区:
医学2区
文献类型:
--
作者:
Ochiai M;Hippo Y;Izumiya M;Watanabe M;Nakagama H

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异型增生在多步骤结肠癌发生中代表癌前状态。虽然诊断需要费力的薄片准备,但我们在此表明,新定义的异常隐窝病灶(ACF)只是标记了整个结肠上的大部分不典型增生。具体地说,在对经典ACF(CACF)评分后,对偶氮甲烷处理的大鼠结肠进行脱色,结果显示了仍被浓染的异常隐窝的子集。它们在形态上被分成三种亚型,其中两种管腔开口受压被证明与异型增生高度相关。因此,我们将含有两种隐窝亚型之一的病灶命名为异型增生相关性ACF(DACF)。通过将已知的癌前病变的不同检测方法应用于同一结肠,我们发现大多数DACF已经被确认为CACF,少数新发现的DACF包含整个人群中更晚期的病变,如扁平的ACF和粘蛋白耗竭的病灶。因此,CACF和DACF的综合评分能够捕捉到结肠的所有早期病变。此外,94%的DACF表现为异型增生,90%的异常增生性病变被证实为DACF。因此,DACF是异型增生的一个有前景的标记物,可能有助于准确识别结肠癌发生的早期阶段。
Dysplasia represents a preneoplastic status in multistep colon carcinogenesis. Whereas laborious preparation of thin sections is required for its diagnosis, we here show that newly defined aberrant crypt foci (ACF) simply mark the majority of the dysplasia on the whole colon. Specifically, decoloring of the azoxymethane-treated rat colon after scoring classical ACF (cACF) resulted in visualization of a subset of aberrant crypts that remained densely stained. They were morphologically classified into three subtypes, of which two with compressed luminal openings proved highly correlated with dysplasia. Accordingly, we designated those foci harboring either of the two crypt subtypes as dysplasia-associated ACF (dACF). By serially applying different detection methods for known preneoplastic lesions to the same colon, we showed that most dACF had already been identified as cACF, and a few newly identified dACF contained an entire population of more advanced lesions, such as flat ACF and mucin-depleted foci. Consequently, integrative scoring of cACF and dACF enabled capture of all early lesions of the colon. Furthermore, 94% of the dACF showed dysplasia and 90% of the dysplastic lesions proved to be dACF. Thus, dACF is a promising marker for dysplasia, likely facilitating precise identification of the early stages of colon carcinogenesis.
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