Bendardaf Riyad, Sharif-Askari Fatemeh Saheb, Sharif-Askari Narjes Saheb, Syrjänen Kari, Pyrhönen Seppo
Oncology unit, University Hospital Sharjah, Sharjah, United Arab Emirates.
Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
Anticancer Res. 2018 Nov;38(11):6399-6404. doi: 10.21873/anticanres.13000.
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.
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.
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).
Association between MMR-status and VEGF-1 expression predicts clinical outcome in mCRC patients.
背景/目的：伊立替康、氟尿嘧啶和亚叶酸钙（IFL）方案对微卫星高度不稳定（MSI-H）或错配修复蛋白表达缺失（dMMR）的转移性结直肠癌（mCRC）患者的益处尚不确定。本研究调查了肿瘤错配修复状态和血管内皮生长因子-1（VEGF-1）表达与mCRC患者一线IFL方案疗效之间的关联。
这项前瞻性研究分析了1998年8月1日至2003年8月30日在芬兰图尔库大学医院被诊断为mCRC的患者。所有患者均接受术后IFL方案治疗。通过免疫组织化学（IHC）评估错配修复蛋白hMLH1和hMSH2的肿瘤表达以及VEGF-1表达。dMMR肿瘤是指显示错配修复蛋白表达缺失的肿瘤，VEGF-1高表达肿瘤是指显示中度或强细胞质染色的肿瘤。主要终点是肿瘤hMLH1或/和hMSH2缺陷与VEGF-1表达之间的关联；肿瘤错配修复状态与IFL反应率之间的关系是次要终点。
在67例mCRC患者中，29例（43%）为hMLH1或/和hMSH2缺陷型，15例（22%）为错配修复功能正常（pMMR）的mCRC患者。在诊断时，与pMMR肿瘤患者相比，hMLH1或/和hMSH2缺陷型肿瘤患者的VEGF-1表达水平较低（p=0.01）。超过一半（n=17，59%）的dMMR患者对一线IFL方案化疗敏感, 而pMMR患者中只有五分之一（n=3，20%）对IFL方案化疗敏感（p=0.045）。
错配修复状态与VEGF-1表达之间的关联可预测mCRC患者的临床结局。
