TY - JOUR
T1 - Different pattern of allelic loss in Epstein-Barr virus-positive gastric cancer with emphasis on the p53 tumor suppressor pathway
AU - Van Rees, Bastiaan P.
AU - Caspers, Eric
AU - Zur Hausen, Axel
AU - Van den Brule, Adriaan
AU - Drillenburg, Paul
AU - Weterman, Marian A J
AU - Offerhaus, G. Johan A
PY - 2002/10/1
Y1 - 2002/10/1
N2 - Both Helicobacter pylori (HP) and Epstein-Barr virus (EBV) have been implicated in carcinogenesis of the stomach. Fifty-seven gastric carcinomas were tested for microsatellite instability and allelic loss at several tumor suppressor loci using 21 polymorphic microsatellite markers. Furthermore, immunohistochemistry for p53 and DPC4/SMAD4 was performed. Results were analyzed according to HP and EBV status of the tumors, as assessed by immunohistochemistry and RNA in situ hybridization, respectively. Fractional allelic loss was lower in EBV-positive carcinomas (n = 15) when compared to EBV-negative carcinomas (P <0.001). EBV positivity was inversely associated with allelic loss at specific markers on chromosomal arms 5q (APC), 17p (TP53), and 18q (DPC4/SMAD4). Allelic loss at the TP53 locus was not encountered in EBV-positive carcinomas, but occurred in 51% of EBV-negative carcinomas (P <0.005). Moreover, none of the EBV-positive carcinomas showed unequivocal p53 immunopositivity in contrast to 39% of the EBV-negative carcinomas (P <0.01). EBV-status was not related to microsatellite instability. There was no correlation between HP-status and any of the molecular alterations tested. In conclusion, EBV-positive gastric carcinomas follow a distinct pathogenesis at the molecular level, in which p53 is not, or differently inactivated.
AB - Both Helicobacter pylori (HP) and Epstein-Barr virus (EBV) have been implicated in carcinogenesis of the stomach. Fifty-seven gastric carcinomas were tested for microsatellite instability and allelic loss at several tumor suppressor loci using 21 polymorphic microsatellite markers. Furthermore, immunohistochemistry for p53 and DPC4/SMAD4 was performed. Results were analyzed according to HP and EBV status of the tumors, as assessed by immunohistochemistry and RNA in situ hybridization, respectively. Fractional allelic loss was lower in EBV-positive carcinomas (n = 15) when compared to EBV-negative carcinomas (P <0.001). EBV positivity was inversely associated with allelic loss at specific markers on chromosomal arms 5q (APC), 17p (TP53), and 18q (DPC4/SMAD4). Allelic loss at the TP53 locus was not encountered in EBV-positive carcinomas, but occurred in 51% of EBV-negative carcinomas (P <0.005). Moreover, none of the EBV-positive carcinomas showed unequivocal p53 immunopositivity in contrast to 39% of the EBV-negative carcinomas (P <0.01). EBV-status was not related to microsatellite instability. There was no correlation between HP-status and any of the molecular alterations tested. In conclusion, EBV-positive gastric carcinomas follow a distinct pathogenesis at the molecular level, in which p53 is not, or differently inactivated.
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M3 - Article
C2 - 12368194
AN - SCOPUS:0036792534
SN - 0002-9440
VL - 161
SP - 1207
EP - 1213
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 4
ER -