ABSTRACT
Background: The ras gene family (H-ras, N-ras and K-ras) are oncogenes that mutate frequently in human cancer, specially in tumors of the biliary tract and pancreas. Aim: To determine the frequency of K-ras gene codon 12 mutation in pancreatic and biliary tumors. Material and Methods: Samples of 35 gallbladder, 15 ampulla of Vater, 10 biliary tract and 9 pancreatic tumors, were analyzed. The tumor tissue was microdissected from paraffin embedded biopsies. The mutation was detected by a combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results: Overall, 46% of samples had K-ras gene mutations. Mutation frequency was 80, 56, 50 and 29% for ampulla of Vater, pancreatic, biliary tract and gallbladder tumors, respectively. When compared with the rest, gallbladder tumors had a significantly lower frequency of the mutation. Median survival for biliary tract tumors was 6 months, compared with 65 months for gallbladder tumors (p <0.05). Conclusions: Gallbladder carcinoma had the lower frequency of K-ras mutation, when compared with pancreatic, biliary tract and ampulla of Vater tumors.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Carcinoma/genetics , Gallbladder Neoplasms/genetics , Genes, ras/genetics , Mutation , Pancreatic Neoplasms/genetics , Carcinoma/mortality , Carcinoma/pathology , Codon , Gallbladder Neoplasms/mortality , Gallbladder Neoplasms/pathology , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Sex Factors , Survival AnalysisABSTRACT
Background:Promoter genomic DNA methylation is an important inactivation mechanism of tumor suppressor genes. This genetic-molecular pathway for cancer may separate a subset of patients with different prognoses and eventually different responses to specific therapies. Aim: To analyze the methylation pattern of important genes related to different carcinogenic mechanisms in patients with gastric cancer (GC) and the relationship with its morphological features and biological behavior. Material and methods: Forty-seven fresh-frozen GC samples were selected. The methylation-specific PCR (MSP) test was used to analyze promoter methylation status for genes MLH1, CDKN2A (p16), APC, CDH1 (Cadherin E) and FHIT. Follow-up and complete morphological features were obtained for all cases. Results: We found methylation in at least one of the genes studied in 83% of the cases. The frequencies of promoter hypermethylation of MLH1, CDKN2A, APC, CDH1 and FHIT were 31%, 43%, 46%, 80% y 62%, respectively. We found a relationship between APC methylation and good histological differentiation (p=0.03); CDH1 methylation with diffuse type by Lauren and 3 or more metastasic lymph nodes (p <0.05); FHIT, CDKN2A and CDH1 methylation and female condition (p <0.04). We also found a non-significant relationship between CDKN2A methylation and better survival (p=0.07). Conclusions: The high frequency promoter methylation found confirms its importance in gastric carcinogenesis. The finding of alterations in the methylation pattern of genes studied and its association with prognostic factors is a helpful tool in the search for new criteria in clinical and therapeutic decision making.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Promoter Regions, Genetic , DNA Methylation , Genes, Tumor Suppressor , Stomach Neoplasms/genetics , Nucleic Acid Amplification Techniques , Polymerase Chain ReactionABSTRACT
Background: The damaging capacity of Helicobacter pylori is variable and depends, in part, on its genetic polymorphism. Aim: To study H pylori genes vacA, cagA and iceA and the relationship of these genotypes with the features of acute damage in chronic gastritis. Material and methods: Gastric endoscopic biopsies were obtained in 75 adults for pathological study and genetic typification of H pylori by specific PCR. Results: In only 64 cases, complete information was available. In 53 of these, there was H pylori infection demonstrated by PCR. Twenty one percent had infection by two or more H pylori strains, vacA gene had genotypes s2/m2, s1/m1 and s1/m2 in 36, 25 and 8% of cases respectively, cagA gene was present in 49% of infected patients. iceA gene had genotypes iceA 1 ad iceA 2 in 15 and 60% of patients respectively. The presence of cagA or alleles s1/m1 and s1/m2 of vacA gene was directly correlated with polymorphonuclear infiltration and the severity of epithelial damage. The genotype s2/m2 of vacA gene was significantly associated with a milder or absent mucosal damage. No association was found between iceA alleles and the pathological features of gastritis. Conclusions: Alleles of vacA and cagA genes of H pilory are associated with the severity of gastric mucosal damage.