Intest Res.  2021 Jan;19(1):12-20. 10.5217/ir.2019.00133.

Two intertwined compartments coexisting in sporadic conventional colon adenomas

• Rubio CA

• KMID: 2512097
• DOI: http://doi.org/10.5217/ir.2019.00133

Abstract

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.

Keyword

Colon; Conventional adenomas; Evolution; Corrupted crypts; Cell proliferation

Figure

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  Fig. 1. Non-dysplastic crypts with corrupted shapes (CCS) found below the neoplastic tissue of sporadic conventional colon adenomas. (A) Low-power view showing multiple clusters of CCS with adenomatous epithelium (dark) on top (H&E, ×1). (B) For comparison: closer view of the normal colonic mucosa (H&E, ×10) portraying parallel crypts, as “rows of test tubes,” perpendicular to the surface-epithelium-muscularis cells mucosae-axis. (C-E) Detail, sporadic polypoid conventional colon adenomas portraying collections of CCS below the adenomatous epithelium (H&E, ×20). (F-I) Non-polypoid colon adenomas also demonstrating clusters of non-dysplastic crypts with CCS below the adenomatous epithelium (dark) on top (F: H&E, ×4; G: MNF116 a pan-epithelial marker, ×4; H: detail, H&E, ×20; I: detail, MNF116, ×20). (J) Colon adenoma in carcinogen-treated rat. Note CCS below the adenomatous epithelium (dark) on top (H&E, ×1).

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  Fig. 2. Cell proliferation in normal colon crypts and in non-dysplastic crypts with corrupted shaped in colon adenomas. (A) Normal colon mucosa with proliferating cells (PCs); note PC, predominantly in the lower third of the crypt (Ki-67, batch MIB1 ×20). (B-J) Sporadic conventional colon adenomas showing non-dysplastic crypts with corrupted shapes, with relocated PC below the neoplastic tissue. (B-F) (Ki-67, batch MIB1 ×10); (G, H) (Ki-67, batch MIB1 ×20). (I, J) (Ki-67, batch MIB1 ×40).

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  Fig. 3. p53-overexpression in the corrupted shapes (CCS) found underneath the neoplastic epithelium of conventional colon adenomas. (A-H) CCS with p53-upregulated cells at arrows. Note intense p53 upregulation in the neoplastic epithelium on top officiating as internal controls (p53-immunostain; A, C, D: ×10; B: ×4; E, F: ×20; G, H: ×40).

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