Ki-ras MUTATIONS IN ADENOMAS: A CHARACTERISTIC OF CANCER-BEARING COLORECTAL MUCOSA

Abstract

Activating mutations in the Ki‐ras2 oncogene are frequently observed in sporadic colorectal adenomas and their incidence is reported to rise in large and tubulovillous adenomas to values close to those in carcinomas. This study shows that this property is a feature of adenomas growing in large bowel that has already demonstrated its propensity to engender malignant tumours: i.e., bowel in which there is a synchronous carcinoma. Adenomas from cancer‐free bowel do not share this high incidence of Ki‐ras mutations. This difference in mutation incidence between adenomas from cancer‐free and cancer‐bearing patients does not appear to derive from sampling bias relative to adenoma size, site, or patient age, nor is it found in another gene (APC) known to be of importance in adenoma formation. Large, dysplastic adenomas from cancer‐bearing bowel, however, are particularly liable to carry Ki‐ras mutations when they arise in patients over 70 years old. The observations suggest that the role of Ki‐ras mutations may be more subtle than merely enhancing adenoma growth. Adenoma cells of cancer‐prone individuals may suffer more mutational events than those in persons selected as cancer‐free.

Associations of Ki-ras Proto-oncogene Mutation and p53 Gene Overexpression in Sporadic Colorectal Adenomas with Demographic and Clinicopathologic Characteristics

“…In addition, individuals with rectal adenomas were twice as likely to have Ki-ras mutations compared with those with distal colonic adenomas ( Table 2). Univariate analyses of the relationships among adenoma size, degree of dysplasia, histology, and Ki-ras mutation showed positive associations with point estimates similar to those reported in the literature (15)(16)(17)(18)(44)(45)(46)(47)(48)(49)(50)(51). However, because these characteristics are highly correlated, multivariate analysis was required to assess the independent effect of each and showed that the presence of tubulovillous histology (OR, 4.19; 95% CI, 2.62-6.68) or of villous histology (OR, 5.45; 95% CI, 2.28-13.03) was strongly related to Ki-ras mutation as compared with tubular adenomas.…”

Traditional serrated adenoma has two pathways of neoplastic progression that are distinct from the sessile serrated pathway of colorectal carcinogenesis

“…Kim et al 7 observed a considerably lower rate of BRAF mutation in traditional serrated adenomas with conventional adenomatous dysplasia. The KRAS mutation was closely related to villous growth in colon adenomas, 30,31 and thus the mutation may confer a potential of protuberant growth, larger size and adenomatous dysplasia in traditional serrated adenoma. Interestingly, aberrant nuclear expression of b-catenin was detected in traditional serrated adenoma with conventional adenomatous dysplasia/tubullovillous adenoma with serrated feature but not in traditional serrated adenoma with serrated dysplasia.…”

Molecular Validation of the Modified Vienna Classification of Colorectal Tumors

“…25 Carrying out multiple PCR amplifications of the individual exons followed by electrophoretic analyses and sequence determinations is a lengthy and expensive process. 26 Therefore, the other genetic markers used to analyze allelic losses at each chromosomal locus may involve less complex methods to examine the malignant potential of tumor cells. For example, three different markers were necessary to determine an allelic loss at chromosome 18q in the present study, resulting in multiple PCR assays.…”