Cyclooxygenase-2 is an independent prognostic factor in gastric carcinoma patients receiving adjuvant chemotherapy and is not associated with EBV infection.
OBJECTIVE
Cyclooxygenase-2 (COX-2) is believed to be involved in carcinogenesis in patients with chronic gastritis with Helicobacter pylori infection. EBV is detected in approximately 10% of gastric carcinomas and H. pylori induces EBV reactivation in the gastric epithelium. We aimed to evaluate significance of COX-2 in gastric carcinoma occurred in EBV and H. pylori prevalent area.


METHODS
Tissue microarray samples from 457 gastric carcinoma patients who underwent gastrectomy and adjuvant chemotherapy were studied with EBER1 in situ hybridization for EBV and immunohistochemistry for COX-2 and other gastric carcinoma-related proteins (hMLH1, E-cadherin, c-erbB, and cyclin D1).


RESULTS
EBV infection was observed in 10.9% of gastric carcinomas and was associated with proximal tumor location, increased numbers of lymph node, and E-cadherin expression (P < 0.01). COX-2 overexpression was closely associated with intestinal histologic type and lower tumor stage (P = 0.01). Univariate analysis showed that pT, pN, lymph node ratio, American Joint Committee on Cancer stage, numbers of negative lymph nodes, and resection margin <1 cm were significant prognostic factors. The Cox proportional hazards regression analysis indicated that lack of COX-2 expression and resection margin <1 cm were independent prognostic factors for disease-free survival (P = 0.008 and 0.03, respectively) and overall survival (P = 0.01 and 0.007, respectively).


CONCLUSIONS
EBV infection is not associated with COX-2 expression or survival in gastric carcinoma. Lack of COX-2 expression is an independent prognostic factor in both overall and disease-free survival in gastric carcinoma. Our results indicate that COX-2 may play a role in the progression of gastric carcinoma regardless of EBV infection and is closely associated with histologic differentiation and prognosis.
Park
Eun Soo
ES
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Do
In Gu
IG
Park
Cheol Keun
CK
Kang
Won Ki
WK
Noh
Jae Hyung
JH
Sohn
Tae Sung
TS
Kim
Sung
S
Kim
Min-Ji
MJ
Kim
Kyoung-Mee
KM
D017024:Chemotherapy, Adjuvant; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000378:metabolism*; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000821:virology*; D046888:Tissue Array Analysis
D051546:Cyclooxygenase 2