TY - JOUR
T1 - Characterisation of a subtype of colorectal cancer combining features of the suppressor and mild mutator pathways
AU - Jass, Jeremy R.
AU - Biden, Kelli G.
AU - Cummings, Margaret C.
AU - Simms, Lisa A.
AU - Walsh, Michael
AU - Schoch, Estelle
AU - Meltzer, Stephen J.
AU - Wright, Caroline
AU - Searle, Jeffrey
AU - Young, Joanne
AU - Leggett, Barbara A.
PY - 1999
Y1 - 1999
N2 - Background - 10% of sporadic colorectal cancers are characterised by a low level of microsatellite instability (MSI-L). These are not thought to differ substantially from microsatellite-stable (MSS) cancers, but MSI-L and MSS cancers are distinguished clinicopathologically and in their spectrum of genetic alterations from cancers showing high level microsatellite instability (MSI-H). Aims - To study the distribution of molecular alterations in a series of colorectal cancers stratified by DNA microsatellite instability. Methods - A subset of an unselected series of colorectal cancers was grouped by the finding of DNA MSI at 0 loci (MSS) (n = 51), 1-2 loci (MSI-L) (n = 38) and 3-6 loci (MSI-H) (n = 25). The frequency of K-ras mutation, loss of heterozygosity (LOH) at 5q, 17p and 18q, and patterns of p53 and β catenin immunohistochemistry was determined in the three groups. Results - MSI-H cancers had a low frequency of K-ras mutation (7%), LOH on chromosomes 5q (0%), 17p (0%) and 18q (12.5%), and a normal pattern of immunostaining for p53 and β catenin. MSI-L cancers differed from MSS cancers in terms of a higher frequency of K-ras mutation (54% v 27%) (p = 0.01) and lower frequency of 5q LOH (23% v 48%) (p = 0.047). Whereas aberrant β catenin expression and 5q LOH were concordant (both present or both absent) in 57% of MSS cancers, concordance was observed in only 20% of MSI-L cancers (p = 0.01). Conclusions - MSI-L colorectal cancers are distinct from both MSI-H and MSS cancers. This subset combines features of the suppressor and mutator pathways, may be more dependent on K-ras than on the APC gene in the early stages of neoplastic evolution, and a proportion may be related histogenetically to the serrated (hyperplastic) polyp.
AB - Background - 10% of sporadic colorectal cancers are characterised by a low level of microsatellite instability (MSI-L). These are not thought to differ substantially from microsatellite-stable (MSS) cancers, but MSI-L and MSS cancers are distinguished clinicopathologically and in their spectrum of genetic alterations from cancers showing high level microsatellite instability (MSI-H). Aims - To study the distribution of molecular alterations in a series of colorectal cancers stratified by DNA microsatellite instability. Methods - A subset of an unselected series of colorectal cancers was grouped by the finding of DNA MSI at 0 loci (MSS) (n = 51), 1-2 loci (MSI-L) (n = 38) and 3-6 loci (MSI-H) (n = 25). The frequency of K-ras mutation, loss of heterozygosity (LOH) at 5q, 17p and 18q, and patterns of p53 and β catenin immunohistochemistry was determined in the three groups. Results - MSI-H cancers had a low frequency of K-ras mutation (7%), LOH on chromosomes 5q (0%), 17p (0%) and 18q (12.5%), and a normal pattern of immunostaining for p53 and β catenin. MSI-L cancers differed from MSS cancers in terms of a higher frequency of K-ras mutation (54% v 27%) (p = 0.01) and lower frequency of 5q LOH (23% v 48%) (p = 0.047). Whereas aberrant β catenin expression and 5q LOH were concordant (both present or both absent) in 57% of MSS cancers, concordance was observed in only 20% of MSI-L cancers (p = 0.01). Conclusions - MSI-L colorectal cancers are distinct from both MSI-H and MSS cancers. This subset combines features of the suppressor and mutator pathways, may be more dependent on K-ras than on the APC gene in the early stages of neoplastic evolution, and a proportion may be related histogenetically to the serrated (hyperplastic) polyp.
KW - Colorectal adenocarcinoma
KW - Loss of heterozygosity
KW - Microsatellite instability
KW - Ras mutation
KW - Serrated polyp
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U2 - 10.1136/jcp.52.6.455
DO - 10.1136/jcp.52.6.455
M3 - Article
C2 - 10562815
AN - SCOPUS:0033043642
VL - 52
SP - 455
EP - 460
JO - Molecular pathology : MP
JF - Molecular pathology : MP
SN - 0021-9746
IS - 6
ER -