Loss of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in gastric cancers.
OBJECTIVE
DNA-PKcs is one of the DNA repair genes. It was recently found that hyperplasia and dysplasia of the intestinal mucosa and the production of aberrant crypt foci were developed in DNA-PKcs-null mice, and this suggests a suppressive role for DNA-PKcs in tumorigenesis.


METHODS
To investigate the possible relationship between the clinico-pathologic characteristics and the survival of gastric cancer patients, the expression status of DNA-PKcs was determined in 279 consecutive gastric cancers. Immunohistochemical analysis was performed to evaluate the expression levels of DNA-PKcs protein by using the tissue array method.


RESULTS
Out of 279 consecutive gastric cancers, 63 cases (22.6%) showed the loss of DNA-PKcs expression. The loss of DNA-PKcs expression was significantly associated with advanced cancer (p<0.001), lymphatic invasion (p=0.001), lymph node metastasis (p=0.009), and advanced pTNM stage (p=0.009). Univariate survival analysis revealed that patients with the loss of DNA-PKcs expression had significantly poorer survival than those patients with intact DNA-PKcs expression (p=0.004). Moreover, the loss of DNA-PKcs expression was identified to correlate with a lower survival in the subgroup of stage I gastric cancer patients (p=0.037).


CONCLUSIONS
The loss of DNA-PKcs expression was found in 23% of human gastric cancers and this was identified to significantly correlate with poor patient survival, especially for stage I gastric cancer patients.
Lee
Hye Seung
HS
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
Yang
Han-Kwang
HK
Kim
Woo Ho
WH
Choe
Gheeyoung
G