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Comparative Study
. 2011 Apr;13(4):387-392.
doi: 10.1111/j.1463-1318.2009.02159.x.

The role of cell proliferation and crypt fission in adenoma aggressiveness: a comparison of ileoanal pouch and rectal adenomas in familial adenomatous polyposis

O C C Will #  1   2 , M Deheragoda #  2   3 , R K S Phillips  1 , S K Clark  1 , I P M Tomlinson  4
Affiliations
Comparative Study

The role of cell proliferation and crypt fission in adenoma aggressiveness: a comparison of ileoanal pouch and rectal adenomas in familial adenomatous polyposis

O C C Will et al. Colorectal Dis. 2011 Apr.

Abstract

Aim: In patients with familial adenomatous polyposis (FAP), ileoanal pouch cancer is rare whereas rectal cancer is common, despite polyp initiation at the two sites being similar at the molecular level. This study investigated whether the disparity in adenoma aggressiveness reflects underlying differences in histogenesis.

Method: Normal mucosal biopsies and 2-3 mm adenomas from patients with FAP were dissected into individual crypts. Crypt area, morphology, fission and mitoses were analysed for crypts from pouch, rectum and supra-anastomotic ileum. Immunohistochemistry of similar archival samples was performed for lysozyme, β-catenin and TP53 expression.

Results: The morphology of normal crypts was similar at each site, although crypt area differed. The area of normal pouch crypts was intermediate between rectum and ileum. The area of adenomatous crypts of rectum and pouch was similar, but the latter had increased asymmetrical fission. Crypt mitoses were proportional to area in all tissues, but crypt fission was reduced in adenomatous crypts from the rectum compared with the pouch. Pouch adenomas retained lysozyme expression as seen in normal ileum. Nuclear β-catenin accumulation was similar, but TP53 expression was increased in rectal adenomas.

Conclusion: Diminutive polyps from rectum and pouch differ in morphology and proliferation. Aggressiveness in rectal polyps is not conferred by increased crypt proliferation, fission, or activation of the Wnt signalling pathway. Increased TP53 expression suggests other molecular mechanisms may be responsible. While crypt mitoses are proportional to crypt area, the threshold for fission may be site specific, indicating that tissue origin may influence histogenesis and thus malignant potential.

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Figures

Figure 1
Figure 1
Morphology of representative crypts from ileum, pouch and rectum.
Figure 2
Figure 2
Photograph of representative dissected crypts from ileal pouch and rectal adenomas.
Figure 3
Figure 3
Results of crypt dissection (means and standard deviations indicated in graphs 1–3).
Figure 4
Figure 4
β-Catenin immunohistochemistry positivity.
Figure 5
Figure 5
TP53 immunohistochemistry positivity.
Figure 6
Figure 6
Lysozyme expression is retained in ileal pouch adenomas. Rectal adenoma shown on left, ileal pouch adenoma on right.
See this image and copyright information in PMC

References

    1. Nugent KP, Spigelman AD, Phillips RK. Life expectancy after colectomy and ileorectal anastomosis for familial adenomatous polyposis. Dis Colon Rectum. 1993;36:1059–62. - PubMed
    1. Thompson-Fawcett MW, Marcus VA, Redston M, Cohen Z, McLeod RS. Adenomatous polyps develop commonly in the ileal pouch of patients with familial adenomatous polyposis. Dis Colon Rectum. 2001;44:347–53. - PubMed
    1. Church J. Ileoanal pouch neoplasia in familial adenomatous polyposis: an underestimated threat. Dis Colon Rectum. 2005;48:1708–13. - PubMed
    1. Will OC, Robinson J, Günther T, Phillips RKS, Clark SK, Tomlinson I. APC mutation spectrum in ileoanal pouch polyps resembles that of colorectal polyps. Br J Surg. 2008;95:765–9. - PubMed
    1. Cummins AG, Catto-Smith AG, Cameron DJ, Couper RT, Davidson GP, Day AS, Hammond PD, Moore DJ, Thompson FM. Crypt fission peaks early during infancy and crypt hyperplasia broadly peaks during infancy and childhood in the small intestine of humans. J Pediatr Gastroenterol Nutr. 2008;47:153–7. - PubMed

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