Allele loss, replication errors and loss of expression of E-cadherin in colorectal cancers.
BACKGROUND
Loss of E-cadherin expression has been implicated in the development of invasive characteristics in colorectal carcinomas. Failure to express E-cadherin may result from mutations of the E-cadherin gene (HSECAD).


OBJECTIVE
To examine the correlation between E-cadherin expression and genetic changes at HSECAD; and to examine differences in E-cadherin expression and genetic changes at HSECAD between three different groups of colorectal cancer--replication error positive (RER+) sporadic cancers, RER--sporadic cancers and ulcerative colitis associated cancers.


METHODS
Sixty eight colorectal cancers (22 RER+ sporadic cancers, 32 RER- sporadic cancers and 14 ulcerative colitis associated cancers) were studied using immunohistochemistry and for allele loss at the HSECAD locus. Exon 16 of HSECAD contains several mononucleotide repeat tracts which are very similar to microsatellite repeats and which may be susceptible to replication errors (manifest as new alleles). All cases were also examined for new alleles in exon 16.


RESULTS
Absent or decreased E-cadherin protein expression was found in 27 (38%) of 68 colorectal cancers and the pattern of expression did not differ significantly among the three tumour groups. Allele loss occurred at HSECAD in four (10%) of 40 informative cancers and there were no differences between the three subgroups. New alleles at exon 16 were detected in three (14%) of 22 RER+ tumours; no new alleles were detected in RER- or ulcerative colitis associated cancers. Overall, there was no correlation between allelic loss or exon 16 replication errors and immunohistochemical E-cadherin expression.


CONCLUSIONS
(1) Loss of E-cadherin expression probably does not occur as a result of mutation at the HSECAD locus in colorectal cancers. (2) There is no difference in the frequency of loss of heterozygosity at HSECAD among RER+, RER- and ulcerative colitis associated colorectal cancers.
Ilyas
M
M
Cancer Immunogenetics Laboratory, John Radcliffe Hospital, Headington, Oxford.
Tomlinson
I P
IP
Hanby
A
A
Talbot
I C
IC
Bodmer
W F
WF
D000483:Alleles; D015820:Cadherins / Q000032:analysis / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics; D015179:Colorectal Neoplasms / Q000150:complications / Q000235:genetics*; D004261:DNA Replication; D005091:Exons; D017353:Gene Deletion; D006801:Humans; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid
D015820:Cadherins