Bendardaf Riyad, Buhmeida Abdelbaset, Hilska Marja, Laato Matti, Syrjänen Stina, Syrjänen Kari, Collan Yrjö, Pyrhönen Seppo
Department of Oncology and Radiotherapy, Turku University Hospital, University of Turku, Turku, Finland.
Anticancer Res. 2008 Nov-Dec;28(6B):3865-70.
Angiogenesis plays an important role in progression of colorectal carcinoma (CRC). Evidence from preclinical and clinical studies indicates that vascular endothelial growth factor (VEGF) is the predominant angiogenic factor in CRC. Indeed, VEGF is expressed in approximately 50% of CRCs, with minimal to no expression in normal colonic mucosa and adenomas. In this study, the expression of VEGF-1 was examined in stage I-IV CRCs to determine its clinicopathological correlates, and association with the response to treatment and disease outcome.
The present series consisted of tissue samples obtained from 360 patients with stage I, II, III, or IV CRC who had undergone large bowel resection during 1981-1990 at Turku University Hospital. Archival paraffin-embedded CRC tissue samples were used to build up tissue microarray (TMA) blocks and VEGF-1 expression was assessed immunohistochemically using an automated staining system. Three different grading systems were applied to evaluate the expression of VEGF-1.
Seventy percent of patients with stage IV CRC had positive VEGF-1 expression, while 50% and 47%, respectively of patients with stage II and III CRC had positive VEGF-1 expression (p = 0.005). VEGF-1 expression in the left colon and rectum was significantly higher than that in the right colon (61% vs. 45%, respectively) (p = 0.006). Significant statistical correlation (p = 0.04) was found between VEGF-1 and 10-year disease-specific survival: patients who died of the disease more frequently had a VEGF-1-expressing tumour than did those who survived for 10 years.
Quantification of VEGF-1 expression seems to provide valuable prognostic information in CRC, particularly in selecting those patients at high risk for disease progression who are likely to benefit from adjuvant therapy.
血管生成在结直肠癌(CRC)进展中起重要作用。临床前和临床研究证据表明,血管内皮生长因子(VEGF)是CRC中主要的血管生成因子。实际上,VEGF在约50%的CRC中表达,在正常结肠黏膜和腺瘤中极少表达或无表达。在本研究中,检测了I-IV期CRC中VEGF-1的表达,以确定其临床病理相关性,以及与治疗反应和疾病转归的关联。
本系列包括1981年至1990年期间在图尔库大学医院接受大肠切除术的360例I、II、III或IV期CRC患者的组织样本。使用存档的石蜡包埋CRC组织样本构建组织微阵列(TMA)块,并使用自动染色系统通过免疫组织化学评估VEGF-1的表达。应用三种不同的分级系统评估VEGF-1的表达。
IV期CRC患者中70%有VEGF-1阳性表达,而II期和III期CRC患者中分别有50%和47%有VEGF-1阳性表达(p = 0.005)。左半结肠和直肠中VEGF-1的表达明显高于右半结肠(分别为61%对45%)(p = 0.006)。VEGF-1与10年疾病特异性生存率之间存在显著统计学相关性(p = 0.04):死于该疾病的患者比存活10年的患者更常患有表达VEGF-1的肿瘤。
VEGF-1表达的定量似乎为CRC提供了有价值的预后信息,特别是在选择那些可能从辅助治疗中获益的疾病进展高危患者方面。