Histogenesis of human colorectal adenomas and hyperplastic polyps: the role of cell proliferation and crypt fission

Abstract

Background: The histogenesis of human colorectal hyperplastic polyps and colorectal adenomas is poorly understood even now. Method: Human colorectal adenomas, hyperplastic polyps, and normal colorectal mucosae (patients with familial adenomatous polyposis and hereditary non-polyposis colorectal carcinoma were excluded) were obtained during colonoscopy and microdissected into individual crypts. Morphology, cell proliferation characteristics, and fission indices of crypts isolated from these lesions were then studied. Results: Crypts isolated from colorectal adenomas and colorectal hyperplastic polyps were significantly larger (p<0.001) than crypts from normal colorectal mucosae. Crypt fission was an uncommon event in normal colonic mucosae but common in crypts isolated from adenomas and hyperplastic polyps (p<0.001). Analysis of the distribution of mitoses suggested an upward expansion of the proliferation compartment in adenomas to the surface of the crypt with no reversal of proliferating cell distribution, as has previously been described. Conclusions: Sporadic human colorectal adenomas and hyperplastic polyps grow by the process of crypt fission. Expansion of the proliferative compartment was demonstrated in crypts from adenomas, consistent with deregulation of cell cycle control.

PTEN-deficient intestinal stem cells initiate intestinal polyposis

“…Crypt expansion in colon cancer and polyposis can be caused by 'bottom-up' crypt fission (division of an existing crypt starting at its base), or by 'top-down' de novo crypt formation (budding of a new crypt from a crypt or villus) 9,10,[30][31][32][33] . We found that both mechanisms of crypt expansion occurred in PTEN-deficient intestines and were associated with an excessive production of M + ISC/p cells ( Fig.…”

Hath1 Inhibits Proliferation of Colon Cancer Cells Probably Through Up-regulating Expression of Muc2 and p27 and Down-regulating Expression of Cyclin D1

“…Previous studies in the developing brain and inner ear of Math1 knockout mice have shown that cerebellar granule neurons and inner ear hair cells of mice fail to differentiate, respectively (Bermingham et al, 1999;Gazit et al, 2004;Fritzsch et al, 2005;Jones et al, 2006 (Zheng et al, 2000;Shou et al, 2003;Kawamoto et al, 2003). More importantly, targeted deletion of Math1 also resulted mice intestinal secretory cells, including goblet cells, in failure of differentiate (Yang et al, 2001) and Hath1 can induce Muc2 expression (van de Wetering et al, 2002). However, a potential role for Hath1 in colon cancer is not yet clear.…”

“…In the course of human colon carcinogenesis, Muc2 expression has decreased while the numbers of goblet cells reduced (Hamilton, 1992;Hanski et al, 1997). The majority of colon carcinomas produce a little mucin except for mucinous adenocarcinoma and signet-ring cell carcinoma (Hanski et al, 1997;Wong et al, 2002). Some studies have shown that Muc2 was concerned with colon tumors.…”

Biomechanical Modelling of Colorectal Crypt Budding and Fission

“…Within adenomas and hyperplastic polyps it is observed that crypts are elongated and deformed, exhibiting budding and multiple fission events (Araki et al, 1995;Brittan and Wright, 2004;Wong et al, 2002). (Although crypt fission is a normal process in the human colon the rate of crypt division in adenomas is significantly raised).…”