Early-onset gastric carcinomas display molecular characteristics distinct from gastric carcinomas occurring at a later age.
Gastric cancer is thought to result from a combination of environmental factors and accumulation of specific genetic alterations, and consequently mainly affects older patients (>50 years of age). Fewer than 10% of patients present with the disease before 45 years of age and these young patients are thought to develop carcinomas with a different molecular genetic profile from that of sporadic carcinomas occurring at a later age. Forty early-onset gastric carcinoma resection specimens were characterized for microsatellite instability (MSI) and loss of heterozygosity status using 22 polymorphic microsatellite markers. Twenty-four biopsies were additionally evaluated for the presence of MSI. No MSI was observed in any of the cases analysed. Losses were infrequent, but were most common for the D1S234 (26.1%) and D1S1676 (17.4%) markers, flanking the RUNX3 gene; for the p53ALU (23.1%) and TP53 (15.4%) markers, near the TP53 gene; and for the D16S2624 (17.2%) marker, near the E-cadherin (CDH1) gene. All cases with loss of CDH1, as well as 6/7 cases with loss of TP53, displayed aberrant staining of the corresponding proteins, pointing to a functional role for these proteins in early-onset gastric carcinogenesis. No germline CDH1, TP53 or RUNX3 mutations were detected in any of the cases analysed. No correlation was observed between non-functional E-cadherin and the histological type of the tumours analysed. Finally, Epstein-Barr virus was not detected in any of the cases analysed. On the basis of these results, early-onset gastric carcinomas appear to have characteristics distinct from gastric carcinomas occurring at a later age.
Department of Pathology, Academisch Medisch Centrum, Amsterdam, The Netherlands. r.p.carvalho@amc.uva.nl
Ralph
R
Carvalho
Anya N A
AN
Milne
Bastiaan P
BP
van Rees
Eric
E
Caspers
Luís
L
Cirnes
Céu
C
Figueiredo
G Johan A
GJ
Offerhaus
Marian A J
MA
Weterman
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015820:Cadherins / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D015820:Cadherins; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53