K-ras mutations and HLA-DR expression in large bowel adenomas

Abstract

Summary A total of 72 sporadic colorectal adenomas in 56 patients were studied for the presence of point mutations in codons 12 and 13 of the K-ras gene and for HLA-DR antigen expression related to clinicopathological variables. Forty K-ras mutations in 39 adenomas were found (54%): 31 (77%) in codon 12 and nine (23%) in codon 13. There was a strong relationship between the incidence of K-ras mutations and adenoma type, degree of dysplasia and sex. The highest frequency of K-ras mutations was seen in large adenomas of the villous type with high-grade dysplasia. Fourteen out of 15 adenomas obtained from 14 women above 65 years of age carried mutations. HLA-DR positivity was found in 38% of the adenomas, large tumours and those with high-grade dysplasia having the strongest staining. Coexpression of K-ras mutations and HLA-DR was found significantly more frequently in large and highly dysplastic adenomas, although twoway analysis of variance showing size and grade of dysplasia to be the most important variable. None of the adenomas with low-grade dysplasia showed both K-ras mutation and HLA-DR positivity (P=0.004). K-ras mutation is recognised as an early event in colorectal carcinogenesis. The mutation might give rise to peptides that may be presented on the tumour cell surface by class II molecules, and thereby induce immune responses against neoplastic cells.

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.…”

Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma

“…Enriched PCR was used to obtain mutant DNA template. 25 If a mutant product was revealed by restriction analysis, the specific mutation was identified by direct sequencing using an Applied Biosystems (Rotterdam, the Netherlands) 373 DNA sequencer.…”

Detection of Isolated Tumor Cells by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism for K-ras Mutations in Tissue Samples of 199 Colorectal Cancer Patients

“…In the development of sporadic CRC, K-ras mutations occur early and with high incidence (30 -60%) in the multistep process of colorectal carcinogenesis (12). Hot spots for mutations in codons 12, 13, and 61 of the K-ras gene can be used for convenient detection of tumor cells (13,14). A relation between the presence of K-ras mutations in the primary tumor and a poor prognosis has been shown by some studies (15)(16)(17)(18)(19)(20), but not by others (21,22).…”

“…Schimanski et al (24) investigated K-ras mutations in liver biopsies of patients at various CRC stages. A modified PCR-RFLP assay was used for detection, which had been originally established by Norheim-Andersen et al (14). With this method a third of all patients with K-ras mutated primary tumors were found to harbor ITCs showing K-ras mutation in the liver identical to the primary tumor (24).…”