Cancer Res Treat.  2005 Apr;37(2):98-102.

Loss of DNA-dependent Protein Kinase Catalytic Subunit (DNA- PKcs) Expression in Gastric Cancers

• Lee HS
• Yang HK
• Kim WH
• Choe G

Abstract

PURPOSE
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. MATERIALS AND 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). CONCLUSION: 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.

Keyword

Immunohistochemistry; Stomach neoplasms; Survival analysis; DNA-PKcs

MeSH Terms

Aberrant Crypt Foci
Animals
Carcinogenesis
Catalytic Domain*
DNA Repair
DNA-Activated Protein Kinase*
Humans
Hyperplasia
Immunohistochemistry
Intestinal Mucosa
Lymph Nodes
Mice
Neoplasm Metastasis
Stomach Neoplasms*
Survival Analysis
DNA-Activated Protein Kinase

Figure

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  Fig. 1 Microscopic features of the immunohistochemical staining of DNA-PKcs in consecutive gastric cancers. (A) Tissue array slide containing 60 cores (×1.8), (B) DNA-PKcs-positive cancer (×400), and (C) DNA-PKcs-negative cancer (×400).

• 

  Fig. 2 Survival curves calculated using the Kaplan-Meier method. (A) The survival curves showed that DNA-PKcs-negative cancers have an unfavorable prognosis compared to DNA-PKcs positive cancers (p=0.004). (B) In the subgroup of stage I gastric cancer patients, loss of DNA-PKcs expression correlated with a lower survival probability (p=0.037).

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