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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Patients with hMLH1 or/and hMSH2-deficient Metastatic Colorectal Cancer Are Associated with Reduced Levels of Vascular Endothelial Growth Factor-1 Expression and Higher Response Rate to Irinotecan-based Regimen
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Patients with hMLH1 or/and hMSH2-deficient Metastatic Colorectal Cancer Are Associated with Reduced Levels of Vascular Endothelial Growth Factor-1 Expression and Higher Response Rate to Irinotecan-based Regimen

机译：HMLH1或/和HMSH2缺陷型转移性结肠直肠癌的患者与血管内皮生长因子-1表达的降低和对基于Irinotecan的方案的较高反应速率相关

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Background/Aim: The benefit of IFL (irinotecan, fluorouracil and leucovorin) regimen for metastatic colorectal cancer patients (mCRCs) with high levels of microsatellite instability (MSI-H) or loss of mismatch repair (dMMR) protein expression, is uncertain. This study investigated the association of tumour MMR-status and VEGF-1 expression with response to first-line IFL regimen in mCRCs. Patients and Methods: This prospective study analyzed patients diagnosed with mCRC between August 1st, 1998, and August 30th, 2003, at the Turku University Hospital, Finland. All patients received postoperative IFL regimen. Tumour expression of the MMR proteins, hMLH1 and hMSH2, and VEGF-1 expression were assessed by immunohistochemistry (IHC). Tumours with dMMR were those demonstrating loss of MMR protein expression, and tumours with high VEGF-1 expression were those showing moderate or strong cytoplasmic staining. The primary endpoint was the association between tumour hMLH1 or/and hMSH2-deficient and VEGF-1 expression; the relation between tumour MMR-status and IFL response rate was the secondary endpoint. Results: Of the 67 mCRCs patients, 29 (43%) were hMLH1 or/and hMSH2-deficient and 15 (22%) were pMMR mCRCs. At diagnosis, patients with hMLH1 or/and hMSH2-deficient tumours expressed lower levels of VEGF-1 compared to pMMR tumour patients (p=0.01). More than half (n=17, 59%) of those with dMMR were chemosensitive to first-line IFL regimen, while just one-fifth (n=3, 20%) of those with pMMR were chemosensitive to the IFL regimen (p=0.045). Conclusion: Association between MMR-status and VEGF-1 expression predicts clinical outcome in mCRC patients.
机译：背景/目的：IFL（Irinotecan，Fluyouracil和Leucovorin）治疗转移结直肠癌患者（MCRC）的益处，具有高水力疏水素不稳定性（MSI-H）或不匹配修复（DMMR）蛋白表达的丧失是不确定的。本研究研究了肿瘤MMR状态和VEGF-1表达与MCRC中的第一线IFL方案的关系。患者及方法：该前瞻性研究分析了1998年8月1日至2003年8月30日在芬兰图库大学医院之间诊断患有MCRC的患者。所有患者均接受术后IFL方案。通过免疫组织化学（IHC）评估MMR蛋白，HMLH1和HMSH2和VEGF-1表达的肿瘤表达。具有DMMR的肿瘤是展示MMR蛋白表达的损失的那些，具有高VEGF-1表达的肿瘤是显示中等或强细胞质染色的肿瘤。主要终点是肿瘤HMLH1或/和HMSH2缺陷和VEGF-1表达之间的关联;肿瘤MMR状态和IFL响应率之间的关系是辅助端点。结果：67例MCRCS患者，29例（43％）是HMLH1或/和HMSH2缺陷，15（22％）是PMMR MCRCs。在诊断中，与PMMR肿瘤患者相比，HMLH1或/和HMSH2缺陷型肿瘤的患者表达了VEGF-1的较低水平（P = 0.01）。具有DMMR的半（n = 17,59％）对第一线IFL方案进行化学致密化，同时仅与IFL方案的PMMR的第五个（n = 3,20％）化学过敏（P = 0.045）。结论：MMR状态与VEGF-1表达之间的关联预测MCRC患者的临床结果。

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