LOH at the APC/MCC gene (5Q21) in gastric cancer and preneoplastic lesions. Prognostic implications.
The APC/MCC gene (Familial Adenomatous Polyposis) at 5q21 plays a role in colon cancer carcinogenesis. LOH at this locus has also been described in gastric cancer and preneoplastic lesions. The APC locus has been recently related to a cell surface adhesion molecule and its alteration may favour metastatic dissemination. LOH at 5q21 has been associated with poor prognosis in other tumors such as lung cancer. Thirty-six gastric cancers were evaluated for LOH at 5q21 with 2 polymorphic markers from microdissected paraffin-embedded material. All tumors were classified by stage, histologic type, degree of differentiation and survival rates. In 4 cases, intestinal metaplasia cells in the adjacent mucosae were also microdissected. Six cases of moderate-severe gastric dysplasia were also added to the study. LOH was determined in 84% of the informative cases of GC, affecting both early and advanced stages of disease. Genomic instability was assessed in 5 cases, 3 of them associated with LOH. The only case of gastric cancer that did not show LOH or instability at 5q21 was a stage II, poorly differentiated intestinal carcinoma without evidence of recurrence after a 36 month follow-up period (the mean survival rate in our series was 28.3% at 36 months). We also found LOH in 2/6 dysplastic lesions and 1/4 intestinal metaplasias. Our data show that LOH at 5q21 is frequent in gastric cancer and is also present in intestinal metaplasia and dysplastic lesions. LOH at this locus is not a prognostic factor in GC in our study, due to the high incidence of LOH that we found.
Sanz-Ortega
J
J
Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Sanz-Esponera
J
J
Caldes
T
T
Gomez de la Concha
E
E
Sobel
M E
ME
Merino
M J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5; D005260:Female; D017491:Genes, APC; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics*; D015996:Survival Rate