Genetic and biochemical changes in colorectal carcinoma in relation to morphologic characteristics.
A distinct genetic pathway may be involved in the development of polypoid and flat colorectal cancers, two morphologically different cancer subtypes. The present study was undertaken to clarify whether different combinations of some genetic alterations commonly involved (such as K-ras and p53 gene mutations) may exist between polypoid and flat types. In addition, to investigate any different proliferative behavior between the two distinct types of colorectal cancer, we tested the enzymatic activity of ornithine decarboxylase (ODC). A total of 29 polypoid type and 21 flat type colorectal cancers were selected for this study. We investigated K-ras and p53 mutations by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) and single strand conformational polymorphism (PCR-SSCP) analysis, respectively. A radiometric method was used to evaluate ODC activity. K-ras and p53 gene mutations were present in 30 and 48% of cases, respectively. A significant association between the p53 mutation and the flat type of colorectal cancer was detected; on the contrary, no significant difference in frequency of K-ras mutation between polypoid and flat type colorectal cancer was found. A statistically significant difference in ODC activity levels was observed between polypoid and flat types. Moreover, we found that ODC activity was significantly higher in neoplastic tissue than in surrounding normal mucosa in polypoid type colorectal cancer. Different mutation patterns and proliferative behavior were observed in polypoid and flat colorectal malignant tumors. Further studies will be required to ascertain whether the distinct growth appearance of colorectal cancer can affect the outcome and prognosis of patients with this type of malignant disease.
Notarnicola
Maria
M
Laboratory of Biochemistry, Scientific Institute for Digestive Diseases 'S. de Bellis', 70013 Castellana G., Bari, Italy.
Linsalata
Michele
M
Caruso
Maria Gabriella
MG
Caruso
Maria Lucia
ML
Altomare
Donato
D
Lorusso
Dionigi
D
Leo
Silvana
S
Di Leo
Alfredo
A
D000368:Aged; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D018450:Disease Progression; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D009154:Mutation; D009955:Ornithine Decarboxylase / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D011123:Polyploidy; D011379:Prognosis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D004247:DNA; D009955:Ornithine Decarboxylase