Aug 28, 2011 - familial adenomatous polyposis. We read with great interest the paper by. Lewis et al1 on the association between increased expression of ...
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Gut Online First, published on August 28, 2011 as 10.1136/gutjnl-2011-300833 PostScript
LETTER
Stem cell markers characterise familial adenomatous polyposis We read with great interest the paper by Lewis et al1 on the association between increased expression of stem cell markers, including leucine-rich repeat-containing Gprotein-coupled receptor 5 (Lgr5), Musashi-1, Bmi1 and CD44, and the severity of intestinal polyposis in Apc1322T mice, which had a submaximal level of active/nuclear b-catenin. Their findings deserve to be validated in clinical specimens. Patients with familial adenomatous polyposis (FAP) who have adenomatous polyposis coli (APC) mutations in the germline can be divided into a classic and a less aggressive variant or attenuated type.2 During adenoma development, APC mutations lead to clonal expansion of the crypt basal mutant stem cells to form colonic adenomas and carcinomas.3 We performed immunohistochemistry staining of CD44, Lgr5, Sox2 and b-catenin on serial sections representing both normal-appearing and adenomatous crypts in 25 samples obtained from an 18-year-old patient with classic FAP and a 51-year-old patient with attenuated FAP. Colonic crypts were scored as positive for a stem cell marker if any immunostaining (weak, moderate or strong) was present and negative if immunostaining was absent, following published work. Nuclear b-catenin staining was scored as positive for active b-catenin expression. Multiple fields under 3200 magnification for normal-appearing mucosa (n¼10) and microadenomas/adenomas (n¼15) were assessed. The percentage of crypts with positive staining for each marker was calculated according to the following formula:
Figure 1 Comparison of distribution of stem cell markers between classic and attenuated FAP.
Figure 2 Concordant immunoreactivity of stem cell markers and nuclear b-catenin in classic FAP.
positive crypt rate (%)¼100%3number of crypts with positive staining/number of total crypts assessed. Classic FAP had a significantly higher number of crypts expressing stem cell markers than matched, normal-appearing mucosa (mean 97.268.3 vs 47.2620.9, p
