Detection of the cytochrome P450 enzyme in lung cancer may be useful for cancer screening

[前言]细胞色素P450(CYP)与肿瘤的发生发展、抗癌前药的激活及其代谢清除有关。最近，一些细胞色素P450，特别是细胞色素P3A亚家族的酶(细胞色素P3A4、细胞色素P3A5和细胞色素P3A7)被发现在许多抗癌药物的代谢中起作用。细胞色素P3A不仅能使他莫昔芬、紫杉醇、长春花碱等主要抗癌药物失活，还能激活环磷酰胺、异环磷酰胺等主要抗癌前体药物。为了更好地处理肺癌，有必要了解细胞色素P450的作用以及它们的表达与肺癌个体临床特征的关系。本研究探讨了78例非小细胞肺癌组织中4种细胞色素P450蛋白(细胞色素P4501A1、细胞色素P42A6、细胞色素P42E1A和细胞色素P3A 3A)的表达及其相互关系、肿瘤P53蛋白表达和临床特征。[材料与方法]对78例非小细胞肺癌组织中的细胞色素P53蛋白和P53 I…进行检测。78名日本NSCLC患者在获得适当的知情同意后在UOEH接受了手术切除，他们的免疫反应更强。肿瘤按WHO分类(腺癌48例，鳞癌30例)进行组织学分型。采用免疫组织化学LSAB法对78例非小细胞肺癌进行免疫组织化学染色。当肿瘤细胞染色超过10%时，细胞色素P53和细胞色素P53表达均为阳性。[结果]48例腺癌组织中，细胞色素P4501A1(43.8%)、细胞色素P42A6(22/48)、细胞色素P42E1(39.6%)和细胞色素P3A(39.6%)阳性，而30例鳞癌组织中无细胞色素P53蛋白阳性表达。女性腺癌中Cyps阳性率明显高于男性腺癌。早期腺癌的CyPS阳性率明显高于晚期腺癌。高分化腺癌和中分化腺癌的Cyps阳性率明显高于低分化腺癌。在腺癌组织中，细胞色素P4501A1、细胞色素P2E1和细胞色素P3A的表达呈正相关。[结论]我们的研究结果提示，更好地了解CYP在肿瘤中的表达是有用和必要的，1)探讨肿瘤的发生机制，2)将CYP表达作为肿瘤标记物，3)将CYP表达用于分子靶向治疗，4)抗癌药物的选择。较少

[Introduction] The cytochrome P450 (CYP) is associated with tumor development and progression as well as activation of anti-cancer prodrugs and their metabolic clearance. Recently, some CYPs, in particular enzymes of the CYP3A subfamily (CYP3A4, CYP3A5, and CYP3A7), have been found to play a role in the metabolism of many anticancer drugs. CYP3A not only inactivates major anticancer drugs, such as tamoxifen, taxol and vinca alkaloids, but also activates major anticancer prodrugs, such as cyclophosphamide and ifosphamide. For the better management of lung cancer, it is essential to understand the roles of CYPs and the relationships between their expression and the clinical feature of individual lung cancers. In this study, we investigate the expression of four CYPs (CYP1A1, CYP2A6, CYP2E1 and CYP3A) in 78 non-small cell lung cancer (NSCLC) and their relationships to each other, tumor p53 expression, and clinical features of the patients.[Materials and Methods] We examined CYPs and p53 i … More mmunoreactivities in 78 Japanese patients with NSCLC who underwent surgical resection at UOEH after obtaining appropriate informed consent. Histological typing of the tumors was performed according to the WHO classification (adenocarcinoma ; 48 cases, squamous cell carcinoma ; 30 cases). Immunohistochemical staining (IHC) of 78 NSCLC was performed by the LSAB (labelled streptavidine biotin) method. CYPs and p53 expression was determined as positive when more than 10% of tumor cells were stained. The p53 mutations in 48 adenocarcinomas were sequenced by the dideoxy chain termination method using an ABI 373A DNA Sequencer (Applied Biosystems).[Results] The CYP1A1, CYP2A6, CYP2E1 and CYP3A positive rates in 48 adenocarcinomas were 43.8% (21/48), 45.8% (22/48), 39.6% (19/48) and 39.6% (19/48), respectively, although there was no CYPs positive cases in 30 squamous cell carcinomas. The CYPs positive rates in female adenocarcinoma were higher than those in male adenocarcinoma. The CYPs positive rates in early adenocarcinoma were higher than those in advanced adenocarcinoma. The CYPs positive rates in well and moderately differentiated adenocarcinoma were higher than those in poorly differentiated adenocarcinoma. There were positive relationships among CYP1A1, CYP2E1 and Cyp3A expressions in adenocarcinoma. The CYPs expression in adenocarcinoma was independent of tumor p53 alterations.[Conclusions] Our results suggest that better understanding of CYP expression in tumors should be useful and essential, 1) to investigate the mechanism of carcinogenesis, 2) to apply CYP expression as tumor marker, 3) to use the knowledge of CYP expression for molecular targeting therapy, 4) for selection of anti-cancer drug. Less