ras Gene mutations and expression of Ras signal transduction mediators in gastric adenocarcinomas.
OBJECTIVE
To investigate ras gene alteration in human gastric adenocarcinomas and its potential relationship to ras signal transduction mediators.


METHODS
Genomic DNA from 104 gastric tumors were analyzed by sequencing of polymerase chain reaction-amplified products for the presence of ras mutations. All the samples were further investigated with the use of immunohistochemical analysis for ERK1 and ERK2.


METHODS
Tertiary care teaching hospital.


METHODS
Seventy patients from a Korean population and 34 from a Midwestern US population composed of white Americans and African Americans.


RESULTS
Fifteen tumors (14%) were positive for either H-ras or K-ras mutation: 9 (13%) of 70 Korean patients and 6 (18%) of 34 US patients. Seven (78%) of the 9 mutated tumors from Korean patients and all 6 (100%) from the US patients were intestinal-type lesions. Either ERK1 and/or ERK2 was overexpressed in 68 samples (65%). No association was established between ras mutations and overexpression of ERK1/2. However, the correlation between ERK1/2 and progression (early vs late) was statistically significant (P =.007).


CONCLUSIONS
These data suggest that ras mutations are uncommon in gastric adenocarcinomas and that differing racial and/or geographic mechanisms may not underlie ras gene alteration. Most ras mutations were, however, observed in the group of intestinal-type samples, supporting the different genetic mechanisms of carcinogenesis between the intestinal- and diffuse-type tumors. It is noteworthy that enhanced ERK1/2 activity could be one of the characteristics of tumor invasiveness in gastric cancers.
Department of Pathology, St Vincent's Hospital, Catholic University, Suwon, Kyungkido, South Korea.
Jinyoung
J
Yoo
Sonya Y
SY
Park
Robert A
RA
Robinson
Seok Jin
SJ
Kang
Woong Shick
WS
Ahn
Chang Suk
CS
Kang
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D011905:Genes, ras; D020022:Genetic Predisposition to Disease; D006801:Humans; D007124:Immunoenzyme Techniques; D007723:Korea; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016376:Oligonucleotides, Antisense; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D014481:United States
D004273:DNA, Neoplasm; D016376:Oligonucleotides, Antisense; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)