大肠癌组织血管生成与患者外周血CK_(20) mRNA表达的临床研究

Clinical research on angiogenesis in colorectal carcinoma and expression of CK_(20)mRNA in peripheral blood

目的观察大肠癌组织中微血管密度、血管内皮细胞生长因子(VEGF)表达与大肠癌患者外围血癌细胞微转移的关系。方法采用S P免疫组织化学法检测了58例大肠癌组织中的微血管密度(MVD)和VEGF的表达,用巢式RT PCR法检测了大肠癌患者外周血中癌细胞微转移情况并分析其与病理指标的关系。结果58例大肠癌组织中35例高中分化MVD计数为30.2±12.7,低分化大肠癌23例MVD计数为86.6±19.1;26例大肠癌组织中VEGF呈阳性染色(44.8%)。MVD计数及VEGF阳性表达与大肠癌分化程度、Dukes分期、有无区域淋巴结转移及远处转移密切相关(P<0.05或P<0.01)。58例大肠癌患者外周血中32例CK20mRNA阳性表达(32/58),术后48h有35例阳性表达(35/58),其中根治性切除组有21例阳性表达(21/44),非根治性手术组12例阳性表达(12/14),21例根治性切除患者术后7～14d有11例转为阴性,12例非根治性切除患者术后7～14d有11例阳性表达。CK20mRNA阳性表达与大肠癌病理分化程度无关,但与Dukes分期、区域淋巴结转移及远处转移情况相关(P<0.01)。CK20mRNA阳性表达患者大肠癌组织中MVD计数(88.5±15.1)与VEGF阳性表达率(65.6%)明显高于CK20mRNA阴性表达患者的MVD计数(31.0±12.9)和VEGF阳性表达率(19.2%)(分别P<0.01,P<0.001)。

Objective To investigate the correlation between microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in tissues of colorectal carcinoma and the micrometastasis of tumor cells in these patients' peripheral blood. Methods The MVD and expression of VEGF were evaluated immunohistochemically while the micrometastasis of tumor cells in these patients' peripheral blood was detected by RT-PCR method. Results The average count of MVD in high and middle differentiation grade was 30.2±12.7, while in low differentiation grade 86.6±19.1. The expression of VEGF was positive in 26 patients(44.8%). The MVD and positive expression of VEGF were correlated to differentiations. stage and metastasis of colorectal carcinoma. CK_~20 mRNA was found in peripheral blood of 32 patients(55.2%) and the positive rate was up to 60.4% 48 hours after operation, among which positive rate in the radical resection group was 47.7% and in the non-radical resection group 85.7%. 11 out of 21 patients positive in CK_~20 mRNA turned to negative 7-14d after radical resection, while 11 out of 12 patients remained positive at the same time after non-radical resection. The expression of CK_~20 mRNA was correlated to the stage and metastasis of the cancer. The MVD and positive expression of VEGF were higher in patients with positive expression of CK_~20 mRNA. Conclusions The MVD and positive expression of VEGF were correlated to differentiation, stage and metastasis of colorectal carcinoma. The angiogenesis in tissues of colorectal carcinoma was closely related to the micrometastasis of tumor cells in these patients' peripheral blood. The detecting of CK_~20 mRNA by RT-PCR may be a sensitive method for evaluating the micrometastasis colorectal carcinoma in peripheral blood and help in prognosis prediction, effect assessment and guidance of multipurpose therapy.