Department of 1Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Anticancer Res. 2012 Sep;32(9):3869-74.
The enzyme Cytochrome P450 2W1 (CYP2W1) is found in fetal colon tissue and is also detected in colorectal cancer but not in non-transformed tissue. In a pilot study, we reported that the immunohistochemically-detected expression of CYP2W1 might be of prognostic value since high expression of CYP2W1 was indicative of a worse prognosis. The aim of this study was to validate the pilot study's results using a larger, independent group of patients with colon cancer.
Immunohistochemical detection of CYP2W1 in 235 malignant colon tumors of stage II and III, was carried out using a polyclonal antibody. Grading of staining was carried out by two independent readers. The highest grade that involved more than 5% of the tumor area on each slide was used for the classification of CYP2W1 expression.
CYP2W1 was expressed at high levels in 30% of the tumors. In the entire colon cancer group it was an independent prognostic factor in multivariate analysis (p=0.04), where high expression (grade 3) correlated with worse outcome. CYP2W1 expression was an independent prognostic factor in the subgroup of patients with colon cancer stage III (p=0.003), but not for those with stage II. In 107 cases, two slices from different areas of the same tumor were available, and no significant difference in CYP2W1 expression between the slices was observed (r=0.53, p<0.001).
The results of the current study were in agreement with those of the previous pilot study and show that higher expression of CYP2W1 seems to be of prognostic value in colon cancer. Furthermore, we found equal expression in slices from two different areas of the same tumor. Since the CYP2W1 enzyme has been shown to catalytically activate compounds to cytotoxic products, the enzyme might be used as a novel drug target for the treatment of colon cancer.
细胞色素 P450 2W1(CYP2W1)酶存在于胎儿结肠组织中,也在结直肠癌中检测到,但在非转化组织中未检测到。在一项初步研究中,我们报告说,CYP2W1 的免疫组织化学检测表达可能具有预后价值,因为 CYP2W1 的高表达表明预后更差。本研究的目的是使用更大的、独立的结肠癌患者组验证初步研究的结果。
使用多克隆抗体对 235 例 II 期和 III 期恶性结肠肿瘤进行 CYP2W1 的免疫组织化学检测。两位独立的读者对染色进行分级。每张幻灯片上涉及肿瘤面积超过 5%的最高等级用于 CYP2W1 表达的分类。
CYP2W1 在 30%的肿瘤中高表达。在整个结肠癌组中,它是多变量分析的独立预后因素(p=0.04),其中高表达(3 级)与较差的预后相关。CYP2W1 表达是结肠癌 III 期患者亚组的独立预后因素(p=0.003),但不是 II 期患者。在 107 例中,两个来自同一肿瘤不同区域的切片可用,并且在切片之间未观察到 CYP2W1 表达的显著差异(r=0.53,p<0.001)。
当前研究的结果与之前的初步研究一致,表明 CYP2W1 的高表达似乎对结肠癌具有预后价值。此外,我们发现同一肿瘤的两个不同区域的切片表达相等。由于 CYP2W1 酶已被证明能催化激活化合物产生细胞毒性产物,因此该酶可作为治疗结肠癌的新型药物靶点。