If a mutation of c-K-ras 2 gene is an important component in the formation of adenocarcinoma, these results did not confirm the successive development from adenomas with severe atypia to advanced carcinomas as the main route for colorectal carcinogenesis in familial adenomatous polyposis patients.
Mutant c-K-ras genes were detected in about 75% of adenocarcinomas of the pancreas (n = 84); 40% of adenomas (n = 72) and carcinomas (n = 244) of the colon end rectum; 30% of carcinomas of the bile duct (n = 19); 25% of carcinomas of the lung (n = 92), and in lower frequency in other carcinomas, including liver, stomach, and kidney.
In contrast, a higher percentage (16/20 = 80%) of pancreatic adenocarcinomas contained mutations in c-Ki-ras 2, despite a lower frequency of DNA aneuploidy in these neoplasms.
These results indicate that activation of the ras gene was not frequent (17%) in human lung cancers, that among these lung cancers mutation of the ras gene was most frequent in adenocarcinomas (27%) and 73% of the point mutations were in the c-Ki-ras2 gene in codon 12, 13, 18 or 61.
Mutant c-K-ras genes were found at the time of initial clinical presentation in the majority of pancreatic adenocarcinomas, suggesting an important role of the mutation in oncogenesis.
The frequency of Ki-ras gene mutations was studied in 100 paraffin-embedded sections obtained from 63 pancreatic adenocarcinomas by in vitro amplification of target sequences via polymerase chain reaction (PCR) and selective oligonucleotide hybridization.
Codons 12, 13 and 61 of the K-ras gene in 120 surgically resected pulmonary adenocarcinomas were examined by the mutation-allele-specific amplification method.
We searched for K-ras gene mutations and HPV type-16 and -18 sequences in 67 primary adenocarcinomas of the uterine cervix by analyzing DNAs from formalin-fixed, paraffin-embedded tissue samples.
As to the prognosis, there were no significant differences between the p53 gene alteration-positive and -negative cases in both the younger and older groups as well as in all subjects, while a tendency of poorer prognosis was observed in K-ras gene alteration-positive cases than for the -negative ones with adenocarcinomas.
Eight of 22 prostate adenocarcinomas (three of nine (33.3%) from the ventral lobe and five of 13 (38.5%) from the dorsolateral lobe, including three transplantable tumors) and one of 11 seminal vesicle adenocarcinomas (9.1%) demonstrated point mutations in the Ki-ras gene.
In addition, point mutations of the c-Ki-ras gene were detected in 1 gastric-type adenocarcinoma and 2 intestinal-type adenocarcinomas, suggesting the occurrence of a common genetic abnormality.
HPV DNA type 16 or 18 in cervical adenocarcinomas was detected in 35% of cases by PCR and in 29% by Southern blotting, and, in contrast to the p53 mutations, the majority of cases with the HPV DNA were at a relatively early clinical stage with low-grade histological atypia. c-Ki-ras gene mutation was detected in only 4% of cervical adenocarcinomas.
Seventy-seven pancreatic adenocarcinomas (60 Spanish and 17 Italian) were tested for Ki-ras gene mutations by analysis of polymerase chain reaction amplified sequences.
Eight pancreatic adenocarcinomas in the range 1.2-3 cm were analyzed for c-K-ras mutation at codon 12 by amplifying the c-K-ras gene around codon 12 out of paraffin-embedded tissue sections using the polymerase chain reaction. c-K-ras mutations were detected by allele-specific oligonucleotide hybridization.
One hundred ninety-four consecutive primary, recurrent, and metastatic colorectal adenocarcinomas, accessioned during 1991 at Rhode Island Hospital, were classified according to the presence and specific type of K-ras-2 point mutation.