Rubio Carlos A
Gastrointestinal Research Laboratory, Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden.
Intest Res. 2021 Jan;19(1):12-20. doi: 10.5217/ir.2019.00133. Epub 2020 Feb 24.
Sporadic conventional colon adenomas are microscopically built of 2 intertwined compartments: one on top, harboring the dysplastic tissue that defines their histo-biomolecular attributes, and the other below, composed of non-dysplastic crypts with corrupted shapes (CCS). The CCS of 306 colon adenomas revealed asymmetric, haphazardly-distributed proliferating cell-domains (PC). In contrast, the PC-domains in normal controls were symmetric, being limited to the lower thirds of the crypts. In 28% out of 501 sporadic conventional adenomas, foci of p53-upregulated dysplastic tissue were found. The CCS in 30% of 108 sporadic adenomas showed p53-upregulated single cells, suggesting mounting somatic mutations. No p53-upregulated cells were found in the crypts of controls. In polypoid adenomas, the mucosa of the stalk without dysplastic tissue on top disclosed CCS with asymmetrical PC-domains and single p53-upregulated cells. The latter observations suggested that CCS had developed prior to and not after the growth of the dysplastic tissue on top. CCS were also found below colon adenomas in carcinogen-treated rats. It is concluded that the 2 intertwined histo-biological compartments of sporadic conventional colon adenomas are probably interdependent components. These findings may open new directions aimed to uncover the link between the normal colonic mucosa and the histogenesis of, conventional adenomas.
上部包含定义其组织生物分子特征的发育异常组织,下部由形状异常的非发育异常隐窝(CCS)组成。对306个结肠腺瘤的CCS进行观察,发现增殖细胞区域(PC)呈不对称、随机分布。相比之下,正常对照的PC区域是对称的,局限于隐窝的下三分之一处。在501个散发性传统腺瘤中,有28%发现了p53上调的发育异常组织灶。在108个散发性腺瘤的30%中,CCS显示有p53上调的单个细胞,提示体细胞突变增加。在对照的隐窝中未发现p53上调的细胞。在息肉状腺瘤中,顶部无发育异常组织的蒂部黏膜显示出具有不对称PC区域和单个p53上调细胞的CCS。后一观察结果表明,CCS在顶部发育异常组织生长之前而非之后就已形成。在致癌物处理的大鼠结肠腺瘤下方也发现了CCS。结论是,散发性传统结肠腺瘤的两个相互交织的组织生物学部分可能是相互依存的成分。这些发现可能为揭示正常结肠黏膜与传统腺瘤组织发生之间的联系开辟新的方向。