Soumaoro Labile Togba, Uetake Hiroyuki, Higuchi Tetsuro, Takagi Yoko, Enomoto Masayuki, Sugihara Kenichi
Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Clin Cancer Res. 2004 Dec 15;10(24):8465-71. doi: 10.1158/1078-0432.CCR-04-0653.
Recent studies have shown that cyclooxygenase (Cox)-2 may be involved in colorectal carcinogenesis. We aimed to determine whether Cox-2 expression in itself can predict outcome of colorectal cancer patient after surgery. In addition, the expression of Cox-1 was also evaluated.
Tissue samples of primary and secondary tumors from 288 patients undergoing surgical resections for colorectal adenocarcinoma were immunohistochemically examined for Cox-2 and Cox-1 expressions. The specimens were graded based on the intensity and extent of staining; then, the correlations between Cox-2 and Cox-1 expressions with clinicopathologic parameters and survival time were analyzed.
Expression of Cox-2 was positive in 70.8% of primary tumor, 92.0% of lymph node metastases, 100.0% of hepatic metastases, and was significantly associated with tumor size, depth of invasion, lymph node metastasis, vessels invasion, stage and recurrence. In contrast, Cox-1 was positive in 42.7% of primary tumor, 84.0% of lymph node metastases, 37.5% hepatic metastases, and was associated with only tumor size. Patients with Cox-2-positive tumors had a significant shorter survival time than those with negative tumors did (P = 0.0006 by log-rank test); and, in a multivariate analysis, Cox-2 was an independent prognostic factor (P = 0.0103; relative risk 4.114; 95% confidence interval, 1.397-12.120). Cox-1 status had no statistically effect on patient survival time.
Elevated Cox-2 expression, but not that of Cox-1, was significantly associated with reduced survival and recognized as an independent prognostic factor in our cohort of colorectal cancer patients.
近期研究表明,环氧化酶(Cox)-2可能参与结直肠癌的发生。我们旨在确定Cox-2自身的表达是否能够预测结直肠癌患者术后的预后。此外,还评估了Cox-1的表达情况。
对288例行结直肠癌手术切除的患者的原发性和继发性肿瘤组织样本进行免疫组织化学检查,以检测Cox-2和Cox-1的表达。根据染色强度和范围对标本进行分级;然后,分析Cox-2和Cox-1表达与临床病理参数及生存时间之间的相关性。
Cox-2在70.8%的原发性肿瘤、92.0%的淋巴结转移灶、100.0%的肝转移灶中呈阳性表达,且与肿瘤大小、浸润深度、淋巴结转移、血管浸润、分期及复发显著相关。相比之下,Cox-1在42.7%的原发性肿瘤、84.0%的淋巴结转移灶、37.5%的肝转移灶中呈阳性表达,仅与肿瘤大小相关。Cox-2阳性肿瘤患者的生存时间显著短于Cox-2阴性肿瘤患者(对数秩检验P = 0.0006);并且,在多变量分析中,Cox-2是一个独立的预后因素(P = 0.0103;相对风险4.114;95%置信区间,1.397 - 12.120)。Cox-1状态对患者生存时间无统计学影响。
在我们的结直肠癌患者队列中,Cox-2表达升高而非Cox-1表达升高与生存时间缩短显著相关,并被认为是一个独立的预后因素。