Expression of DNA Damage Response Markers in Early-Onset or Familial Gastric Cancers

Document Type: Research Articles

Authors

1 Department of Pathology, Chung-Ang Univesity, College of Medicine, Seoul, South Korea.

2 Department of Surgery, Chung-Ang University, College of Medicine, Seoul, South Korea.

3 Department of Internal Medicine, Chung-Ang University, College of Medicine, Seoul, South Korea.

4 Department of Pathology, Seoul National University Bundang Hospital, Seongnam, South Korea.

5 Department of Pathology, Seoul National University, College of Medicine, Seoul, South Korea.

Abstract

Background: Early-onset or familial gastric cancer (GC) is known to have clinicopathologic profiles different from
those of sporadic GC. We aimed to compare DNA damage response marker expression between early-onset or familial
GC and sporadic GC. Methods: GC samples were obtained from patients who underwent gastrectomy for GC at Seoul
National University Hospital. Immunohistochemical analyses of various DNA damage response markers, including
BRCA1, BRCA2, MRE11, RAD51C, and γH2AX, were performed using 54 early-onset GC, 59 familial GC, and 337
sporadic GC tissue microarray samples. Correlations between marker expression and clinicopathologic features were
evaluated by univariate and multivariate analyses, and overall survival was analyzed. Results: The rate of γH2AX
positivity was significantly higher (p < 0.001) in early-onset or familial GC than in sporadic GC. In contrast, the rates of
MRE11 negativity and RAD51C negativity were significantly higher in sporadic GC than in early-onset or familial GC.
BRCA1 negativity was associated with decreased overall survival in sporadic GC (p = 0.002), and MRE11 negativity
was associated with decreased overall survival in sporadic GC (p = 0.012). Conclusion: Our results show significant
differences in DNA damage response marker expression between early-onset or familial GC and sporadic GC.

Keywords

Main Subjects