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Gut. Jul 1998; 43(1): 85–92.
PMCID: PMC1727161

Colonic epithelial cell proliferation in hereditary non-polyposis colorectal cancer

Abstract

Background—Despite the recent discovery of four genes responsible for up to 90% of all cases of hereditary non-polyposis colorectal cancer (HNPCC), there will still be families in whom predictive testing is not possible. A phenotypic biomarker would therefore be useful. An upwards shift of the proliferative compartment in colonic crypts is reported to be one of the earliest changes in premalignant mucosa.
Aims—To assess the role of crypt cell proliferation as a phenotypic biomarker in HNPCC.
Patients—Thirty five patients at 50% risk of carrying the HNPCC gene (21 of whom subsequently underwent predictive testing and hence gene carrier status was known) and 18controls.
Methods—Crypt cell proliferation was measured at five sites in the colon using two different techniques. Labelling index was determined using the monoclonal antibody MIB1 and whole crypt mitotic index was measured using the microdissection and crypt squash technique. The distribution of proliferating cells within the crypts was also assessed.
Results—There were no significant differences in the total labelling index or mean number of mitoses per crypt, nor in the distribution of proliferating cells within the crypt, between the study and control groups at any site. When the 21 patients in whom gene carrier status was known were analysed separately there were no significant differences in the measured indices of proliferation between the HNPCC gene carriers and non-gene carriers.
Conclusion—Crypt cell proliferation is not a discriminative marker of gene carriage in HNPCC.

Keywords: cell proliferation; hereditary non-polyposis colorectal cancer

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Selected References

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Figures and Tables

Figure 1
Comparison of the MIB1 labelling index with the mean number of mitoses per crypt (265 points plotted represent data for 53 patients from five sites).
Figure 2
MIB1 datachanges in the labelling index along the large bowel for the HNPCC 50% risk group and control group.
Figure 3
Microdissection datachanges in the mean number of mitoses per crypt along the large bowel for the HNPCC 50% risk group and control group.
Figure 4
Mean labelling index for all five sites, according to gene carrier status.

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