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Ann Thorac Surg 2006;82:1198-1204
© 2006 The Society of Thoracic Surgeons


Original Articles: General Thoracic

Combined Analysis of Cyclooxygenase-2 Expression With p53 and Ki-67 in Nonsmall Cell Lung Cancer

Hiroyoshi Tsubochi, MDa,*, Nobuyuki Sato, MDb, Misae Hiyama, MDc, Mitsuomi Kaimori, MDc, Shunsuke Endo, MDa, Yasunori Sohara, MDa, Tadashi Imai, MDb

a Department of General Thoracic Surgery, Omiya Medical Center, Jichi Medical School, Omiya, Saitama, Japan
b Department of General Thoracic Surgery, Aomori Prefectural Central Hospital, Aomori, Japan
c Department of Pathology, Aomori Prefectural Central Hospital, Aomori, Japan

Accepted for publication April 19, 2006.

* Address correspondence to Dr Tsubochi, Department of General Thoracic Surgery, Omiya Medical Center, Jichi Medical School, Amanuma-cho 1-847, Omiya, Saitama, 330-8503 Japan (Email: h-tsubochi{at}omiya.jichi.ac.jp).

BACKGROUND: Cyclooxygenase-2 (COX-2) is known to play a role in carcinogenesis and tumor progression. The aim of this study was to evaluate the relationship between COX-2 expression and clinicopathologic features, and to define the importance of COX-2 expression alone and in combination with p53 and Ki-67 expression in the clinical outcome of NSCLC.

METHODS: A total of 219 patients with stage I-IIIB nonsmall cell lung cancer (NSCLC) who previously underwent surgery were analyzed in this study. The COX-2 expression was evaluated by means of immunohistochemistry; p53 and Ki-67 immunoreactivity were also studied.

RESULTS: The COX-2 expression was observed in 137 patients (63%) and was significantly associated with lymph node metastasis and the histological grade of those with adenocarcinoma (p = 0.02 and 0.04, respectively). Kaplan-Meier analyses revealed that COX-2 expression was correlated with poor survival (p = 0.005), whereas multivariate survival analysis did not reveal COX-2 expression to be an independent prognostic factor. When the patients were stratified according to gender, age, tumor histology, and disease stage, COX-2 expression was significantly associated with unfavorable prognosis in males, younger patients (≤ 65 years), and those with adenocarcinoma and stage I tumors. The prognosis of patients with tumors negative for both COX-2 and p53 expression was significantly favorable, whereas those with tumors positive for COX-2 expression and with a high Ki-67 labeling index had a significantly unfavorable prognosis.

CONCLUSIONS: These findings indicate that combined immunohistochemical analysis of COX-2 with p53 and Ki-67 can be useful for identifying the prognosis of NSCLC patients.


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