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 microsatelite-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 beta 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 beta 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 beta 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.
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 microsatelite-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 beta 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 beta 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 beta 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.
Authors: J Jen; S M Powell; N Papadopoulos; K J Smith; S R Hamilton; B Vogelstein; K W Kinzler Journal: Cancer Res Date: 1994-11-01 Impact factor: 12.701
Authors: S Markowitz; J Wang; L Myeroff; R Parsons; L Sun; J Lutterbaugh; R S Fan; E Zborowska; K W Kinzler; B Vogelstein Journal: Science Date: 1995-06-02 Impact factor: 47.728
Authors: A Horii; H J Han; M Shimada; A Yanagisawa; Y Kato; H Ohta; W Yasui; E Tahara; Y Nakamura Journal: Cancer Res Date: 1994-07-01 Impact factor: 12.701
Authors: G B Baretton; F Autschbach; S Baldus; H Bläker; G Faller; H K Koch; C Langner; J Lüttges; M Neid; P Schirmacher; A Tannapfel; M Vieth; D E Aust Journal: Pathologe Date: 2011-02 Impact factor: 1.011
Authors: T Kambara; L A Simms; V L J Whitehall; K J Spring; C V A Wynter; M D Walsh; M A Barker; S Arnold; A McGivern; N Matsubara; N Tanaka; T Higuchi; J Young; J R Jass; B A Leggett Journal: Gut Date: 2004-08 Impact factor: 23.059
Authors: Yoshifumi Baba; Curtis Huttenhower; Katsuhiko Nosho; Noriko Tanaka; Kaori Shima; Aditi Hazra; Eva S Schernhammer; David J Hunter; Edward L Giovannucci; Charles S Fuchs; Shuji Ogino Journal: Mol Cancer Date: 2010-05-27 Impact factor: 27.401