Sporadic gastric carcinomas with microsatellite instability display a particular clinicopathologic profile.
Mutations in recently identified genes on chromosomes 2 and 3 seem to be responsible for repair errors (RER+) throughout the genome. This novel genetic mechanism was first reported in hereditary non-polyposis colorectal cancer syndrome and in cancers that are characteristic of this syndrome, such as carcinomas of the right colon, stomach and endometrium. We investigated the frequency of RER+ phenotype in a series of 34 sporadic gastric carcinomas, in an attempt to see if the RER+ cases displayed any particular morphologic features and/or if they showed distinctive clinicopathologic characteristics. Twelve loci were investigated. We found 23 RER- cases (67.6%) and 11 RER+ cases (32.4%). A significant association was found between RER+ carcinomas and localization of the tumors: 9 of the 11 RER+ carcinomas (81.8%) were located at the antrum whereas all the cardiac tumors were RER-. The RER+ phenotype was also significantly related to the presence of moderate/abundant T-cell lymphoid infiltration within the tumors. The 3-year survival rate of patients with RER+ tumors was suggestively longer than that of patients with RER- tumors. No significant relationship was found between several clinicopathologic characteristics of the cases, including age, sex, staging, histologic type and ploidy, despite a trend towards an association between RER+ phenotype and advanced age of the patients and poorly differentiated, intestinal type of the carcinomas. The high frequency of microsatellite instability in sporadic gastric carcinomas supports the involvement of this genetic mechanism in gastric carcinogenesis. Gastric carcinomas with the RER+ phenotype tend to occur as poorly differentiated adenocarcinomas in the antrum of elderly patients, display abundant T-cell infiltration and carry a relatively good prognosis.
Seruca
R
R
Unit of Genetics, Medical Faculty of Porto, Hospital S. João, Oporto, Portugal.
Santos
N R
NR
David
L
L
Constância
M
M
Barroca
H
H
Carneiro
F
F
Seixas
M
M
Peltomäki
P
P
Lothe
R
R
Sobrinho-Simões
M
M
D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D012091:Repetitive Sequences, Nucleic Acid; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D016019:Survival Analysis
D004273:DNA, Neoplasm; D005819:Genetic Markers