CD44 expression in colorectal adenomas is an early event occurring prior to K-ras and p53 gene mutation.
Neoplastic progression of colorectal epithelial cells from benign adenomas to malignant carcinomas appears to result from a series of genetic alterations involving both oncogenes and tumor suppressor genes. This progression was recently found to be associated with expression of splice variant isoforms of CD44, a cell surface hyaluronate receptor implicated in carcinogenesis. In this study we examined the relationship of CD44 expression to somatic genetic events in the adenoma-carcinoma sequence: point mutation of K-ras in codons 12 and 13 and overexpression of p53 protein as a marker of gene mutation. Among 22 small adenomas, CD44 was present in 9 (41%), of which only 1 contained a K-ras mutation. CD44 was absent in the other 2 small adenomas positive for K-ras mutation or p53 overexpression. In contrast to the early expression of CD44 in small adenomas, mutations of K-ras and p53 were detected preferentially in large adenomas and late-stage adenomas containing carcinoma. The frequent expression of CD44 prior to K-ras and p53 gene alterations in colorectal neoplasia suggests that activation of CD44 gene expression is related to earlier events in the adenoma-carcinoma sequence, possibly cell activation and proliferation following APC gene mutation or alteration of DNA methylation.
Kim
H
H
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Yang
X L
XL
Rosada
C
C
Hamilton
S R
SR
August
J T
JT
D000236:Adenoma / Q000235:genetics* / Q000473:pathology*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis*; D002471:Cell Transformation, Neoplastic; D003062:Codon / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D015870:Gene Expression; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D018960:Hyaluronan Receptors; D009154:Mutation; D009367:Neoplasm Staging; D017354:Point Mutation; D011956:Receptors, Cell Surface / Q000032:analysis / Q000096:biosynthesis*; D016201:Receptors, Lymphocyte Homing / Q000032:analysis / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D003062:Codon; D018960:Hyaluronan Receptors; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing