Ultrastructure of the “transitional” mucosa adjacent to large bowel carcinoma

Riddell, Robert H.; Levin, Bernard

doi:10.1002/1097-0142(197711)40:5+<2509::aid-cncr2820400918>3.0.co;2-k

Cited by 66 publications

(23 citation statements)

References 10 publications

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“…[39][40][41] Bjerknes and Cheng found greatly elongated crypts at the margins of adenomas from MIN mice and these crypts had normal APC function. 42 Our findings correlate well with the mouse data of Bjerknes and Cheng.…”

Section: Discussionmentioning

confidence: 96%

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

Wong

2002

Gut

133

137

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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.

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Section: Discussionmentioning

confidence: 96%

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

Wong

2002

Gut

133

137

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“…Earlier studies, such as those by Filipe and Branfoot (17) and Dawson and Filipe (18), had reported histochemical changes in the mucosa adjacent to and remote from colonic carcinoma. Riddell and Levin (19) found ultrastructural changes in the mucosa adjacent to carcinoma of the colon. Saffos and Rhatigan (20) described light microscopic changes in mucosa adjacent to colonic cancer and Shamsuddin et al (21) described changes in the colonic mucosa adjacent to and remote from cancer of the colon.…”

Section: Introductionmentioning

confidence: 99%

Karyometry of the Colonic Mucosa

Alberts¹,

Einspahr²,

Krouse

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Objective: The study summarizes results of karyometric measurements in epithelial cells of the colorectal mucosa to document evidence of a field effect of preneoplastic development among patients with colorectal adenocarcinoma or adenoma. Methods: Karyometric analyses were done on highresolution images of histologic sections from 48 patients with colorectal adenocarcinomas and 44 patients with adenomas and on images from matching normal-appearing mucosa directly adjacent to such lesions, at a 1-cm and 10-cm distance from the lesions or from the rectal mucosa of adenoma patients, as well as from 24 healthy normal controls with no family history of colonic disease. Results:The nuclei recorded in the histologically normal-appearing mucosa of patients with either colorectal adenoma or adenocarcinoma exhibited differences in karyometric features in comparison with nuclei recorded in rectal mucosa from patients who were free of a colonic lesion. These differences were expressed to the same extent in tissue adjacent to the lesions and in normal-appearing tissue as distant as the rectum. Conclusions: The nuclear chromatin pattern may serve as an integrating biomarker for a preneoplastic development. The field effect might provide an end point in chemopreventive intervention trials. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2704 -16)

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“…The crypts in this transitional region are enlarged and often branched. [1][2][3][4][5] However, as a similar state is observed at the margins of an array of lesions, it is now believed that it represents a reactive state and not a preneoplastic condition 6,7 and has since been largely ignored. We have noticed in studies of a mouse model of familial adenomatous polyposis 8 that although the dysplastic epithelium forming the bulk of adenomas is Apc negative, there is often a layer of Apc-positive nondysplastic crypts underlying the tumor.…”

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confidence: 99%

Colossal Crypts Bordering Colon Adenomas in ApcMin Mice Express Full-Length Apc

Bjerknes

Cheng

1999

The American Journal of Pathology

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Enlarged but nondysplastic crypts are frequently observed at the margins of colon tumors , forming what has been called a transitional epithelium. It is now thought that this is a reactive state and not a preneoplastic condition as previously suggested. We have used the mouse familial adenomatous polyposis model , Apc Min , to study these abnormal adenoma-associated crypts. We report that these nondysplastic crypts are enormous (as much as 10 times normal length) and branch more frequently than normal crypts. They express wild-type Apc protein and display the wild-type Apc allele. We conclude that the colossal crypts at adenoma mar- It has long been recognized that the colonic epithelium at the margins of adenocarcinomas, although not neoplastic, is not normal. The crypts in this transitional region are enlarged and often branched. 1-5 However, as a similar state is observed at the margins of an array of lesions, it is now believed that it represents a reactive state and not a preneoplastic condition 6,7 and has since been largely ignored. We have noticed in studies of a mouse model of familial adenomatous polyposis 8 that although the dysplastic epithelium forming the bulk of adenomas is Apc negative, there is often a layer of Apc-positive nondysplastic crypts underlying the tumor. 9 These Apc-positive crypts are often cut in cross section when the tumor is sectioned orthogonally to the surface. This observation raised questions about the relationship of the Apc-positive crypts to the overlying tumor and to the surrounding normal epithelium. We show here that they represent greatly elongated crypts, with normal Apc gene function, that extend under the tumor from the margins. Materials and Methods Isolation of Intact Epithelium and Scanning Electron MicroscopyFifteen week-old Apc Min mice (Jackson Laboratories, Bar Harbor, ME) were used. Intact epithelium was isolated, from small segments of colon each containing an adenoma, by intraventricular perfusion of 30 mmol/L EDTA in PBS followed by vibration into 4% paraformaldehyde in PBS. 10 After fixation for 30 minutes on ice, the isolated epithelium was washed in PBS and then rinsed and stored in methanol at Ϫ20°C. The colon adenomas and adjacent mucosa were dissected from the vibrated segments and fixed for 30 minutes in 2.5% glutaraldehyde in PBS. The adenomas were then processed for scanning electron microscopy (SEM) by post-fixing in 1% osmium tetroxide in 0.1 mol/L cacodylate HCl buffer, pH 7.4, and then dehydrated through a graded series of ethanol, critical-point dried, 11 and sputter coated with gold palladium. ImmunofluorescenceColossal crypts were microdissected from the isolated epithelium, rinsed in 1% Nonidet P-40 (NP40) in PBS, freeze-thawed at Ϫ20°C to increase permeability, rinsed in 1% NP40, and blocked at room temperature for 1 hour in PBS containing 10% newborn calf serum and 1% NP40. The crypts were incubated overnight at 4°C in rabbit polyclonal antibodies specific for the carboxy terminus of Apc protein (Santa Cruz Biotechnology, Santa Cruz, C...

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Ultrastructure of the “transitional” mucosa adjacent to large bowel carcinoma

Cited by 66 publications

References 10 publications

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

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

Karyometry of the Colonic Mucosa

Colossal Crypts Bordering Colon Adenomas in ApcMin Mice Express Full-Length Apc

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