Impact of Cyclooxygenase-2 Expression on the Survival of Glioblastoma

Purpose: To investigate the degree and effect of cyclooxygenase (COX)-2 expression on the survival of patients with glioblastoma multiforme (GM). Materials and Methods: Between 1997 and 2006, thirty consecutive GM patients treated with surgery and postoperative radiotherapy (dose range: $44{\sim}65.1$ Gy, median dose: 61.2 Gy) were included in the study. Three patients were excluded that discontinued radiotherapy before receiving a dose of 40 Gy due to mental deterioration. The expression of the COX-2 protein in surgical specimens was examined by immunohistochemical analysis. Survival analysis and verification were performed with respect to sex, age, performance status, resection extent, radiotherapy dose, and degree of COX-2 expression using the Kaplan-Meier method and the log rank test. Results: The median length of follow-up was 13.3 months (range:$6{\sim}83$ months). Staining for COX-2 was positive in all patient samples. Staining for COX-2 that was positive for over 75% of the tumor cells was found in 24 patients. Staining for COX-2 that was positive in less than 25% of tumor cells was found in 3 patients (10.0%), staining for COX-2 that was positive in 25 to 50% of tumor cells was found in 1 patient (3.3%), staining for COX-2 that was positive in 50 to 75% of tumor cells was found in 2 patients (6.7%) and staining for COX-2 that was positive in 75 to 100% of tumor cells was found in 24 patients (80.0%). The median survival and two-year survival rate were 13.5 months and 17.5%, respectively. The survival rate was influenced significantly by the degree of resection (tumor removal by 50% or more) and radiotherapy dose (59 Gy or greater) (p<0.05). The median survival of patients with staining for COX-2 that was positive in less than 75% of tumor cells and in at least 75% of tumor cells was 15.5 and 13.0 months, respectively (p>0.05), and the two-year survival for these groups was 33.3 and 13.3%, respectively (p>0.05). Conclusion: The absence of a statistical correlation between the degree of COX-2 expression and survival in GM patients, despite the high rate of COX-2 positive tumor cells in the GM patient samples, requires further studies with a larger series to ascertain the prognostic value of the degree of COX-2 expression in GM patients.

다형성아교모세포종 환자에서 Cyclooxygenase-2 발현이 생존율에 미치는 영향

목적 :다형성아교모세포종 환자들에서 cyclooxygenase-2 (COX-2) 단백의 발현 정도와 생존율에 미치는 영향을 조사하고자 한다. 대상 및 방법: 1997년부터 2006년까지 다형성아교모세포종으로 수술 및 방사선치료를 받은 환자들 중에서, 의식 상태의 악화로 40 Gy 전에 방사선치료가 중단된 3명을 제외한 30명을 대상으로 하였다. 조직에서의 COX-2의 발현은 면역조직화학염색으로 검사하였다. 생존 분석과 성별, 나이, 활동도, 수술 정도, 방사선량, COX-2 발현 정도 등이 생존율에 미치는 영향을 Kaplan Meier 법과 log rank test로 분석 및 검증하였다. 결과: 중앙추적관찰기간은 13.3개월이었다($6{\sim}83$). 전체 환자들에서 COX-2의 발현이 관찰되었고, 종양 세포의 75%이상에서 COX-2가 양성이었던 환자가 24명이었다. 종양 세포의 25%미만, 3명(10.0%); $25{\sim}50%$, 1명(3.3%); $50{\sim}75%$, 2명(6.7%); $75{\sim}100%$, 24명(80.0%). 중앙생존기간이 13.5개월이었고, 2년 생존율은 17.5%없다. 수술 정도(50% 이상 종양 제거)와 방사선량(59 Gy 이상 조사)이 생존율에 유의하게 영향을 주었다(p<0.05). 종양 세포의 75% 미만에서 COX-2가 발현되었던 환자군과 75% 이상에서 발현되었던 환자군에서 중앙생존기간은 각각 15.5개월과 13.0개월이었고(p>0.05), 2년 생존율은 각각 33.3%와 13.3%없다(p>0.05). 결론: 다형성아교모세포종에서의 COX-2 양성도는 높았지만, 다형성아교모세포종 환자들에서 COX-2 발현의 정도와 생존율 간에는 통계적인 유의성이 없었으므로, 향후 보다 많은 환자들을 대상으로 COX-2 발현 정도가 생존율에 미치는 영향에 대한 연구가 필요하다.