Clinical significance of p53, K-ras and DCC gene alterations in the stage I-II colorectal cancers.
OBJECTIVE
Genetic alterations of p53, K-ras and DCC genes have a pivotal role in the colorectal cancer progression. The aim of this study was to clarify the association between K-ras mutations, p53 aberrations and DCC loss of heterozygosity (LOH), with the patient outcome and tumor characteristics in 43 stage I-II colorectal cancer patients.


METHODS
Mutations in exons 5-8 of the p53 gene and codon 12 and/or 13 of the K-ras gene were assayed by PCR-SSCP and then confirmed by DNA sequencing. DCC LOH was studied by PCR-RFLP, while p53 immunohistochemistry was also made.


RESULTS
Mutations of the p53 gene were found in 14 (32.5%) tumors. Five (12%) cases showed mutation of the K-ras gene. Nuclear staining of p53 was found in 22 (51 %) cases. DCC LOH was found in 5 (12%) cases. Cases with guanine to thymine substitution that occurred in K-ras codon 12 and DCC LOH were found to be more aggressive than other cases with codon 12 mutations or DCC wild-type phenotype. Many tumors with p53 over-expression were localized on the left side of the colon (p=0.005). The stage of the tumor was higher in patients who died during the follow-up period, when compared to the ones who have survived.


CONCLUSIONS
Although none of these genetic alterations showed a significant prognostic value, specific mutation of K-ras gene and DCC LOH phenotype might have a predictive prognostic implication in colorectal cancer. Furthermore, different etiopathogenetic mechanisms might be involved in the tumorigenesis of the left and right colon.
Akkiprik
Mustafa
M
Marmara University, School of Medicine, Department of Medical Biology, Tibbyie C. no. 49, 34668 Haydarpasa, Istanbul, Turkey.
Ataizi-Celikel
Cigdem
C
Ataizi-Celikel
Ciddem
C
Düşünceli
Fikret
F
Sönmez
Ozgür
O
Gulluoglu
Bahadir M
BM
Güllüoglu
Bahadýr M
BM
Sav
Aydin
A
Sav
Aydýn
A
Ozer
Ayşe
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D016163:Genes, DCC / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016159:Tumor Suppressor Protein p53