Common occurrence of APC and K-ras gene mutations in the spectrum of colitis-associated neoplasias.
OBJECTIVE
Chronic colitis is associated with an increased risk of colorectal neoplasia, creating a need for early diagnosis in this population. Little is yet known of the genetic changes of early lesions. Cases of colitis-associated neoplasia were analyzed for APC and K-ras mutations with special emphasis given to the spectrum of noninvasive lesions.


METHODS
Ten patients were studied. APC mutations were screened by an in vitro synthesized protein assay, and K-ras mutations were screened by a ligation assay.


RESULTS
APC mutations were found in 5 patients, including dysplasias. K-ras mutations were present in 5 patients and in all classes of lesions, including 5 of 14 lesions indefinite for dysplasia. In only 2 patients were no mutations found.


CONCLUSIONS
Mutations of APC and K-ras are common in colitis-associated neoplasia and can occur early in neoplastic progression. Serrated lesions and lesions indefinite for dysplasia may harbor genetic changes and thus are clonal, highlighting the importance of distinguishing them histologically. Assays for APC and K-ras mutations are promising as adjuncts to surveillance programs. Care will be needed in their application because the confident diagnosis of early lesions presumed to be of lesser clinical importance will raise new issues concerning prudent patient management.
Department of Pathology, Johns Hopkins Hospital and School of Medicine, Baltimore, Maryland.
M S
MS
Redston
N
N
Papadopoulos
C
C
Caldas
K W
KW
Kinzler
S E
SE
Kern
D000328:Adult; D000368:Aged; D001483:Base Sequence; D003092:Colitis / Q000150:complications*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D017491:Genes, APC / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology