Angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: NOTCH1 detrimental to overall survival

BMC Cancer

Research Article

Alexandre André Balieiro Anastácio da Costa¹  Victor Hugo Fonseca de Jesus¹  Raul Amorim Marques¹  Tadeu Ferreira Paiva¹  Vladmir Cláudio Cordeiro de Lima²  Mariana Petaccia de Macedo³  Maria Dirlei Begnami³  Patricia Maria Peresi³  Aline Damascena⁴  Benedito Mauro Rossi⁵ 

[1] Department of Medical Oncology, A. C. Camargo Cancer Center, São Paulo, Brazil;Department of Medical Oncology, A. C. Camargo Cancer Center, São Paulo, Brazil;Department of Clinical Oncology, 1° Subsolo, Edifício Hilda Jacob R. Prof. Antônio Prudente, 211, ZC 01509-900, São Paulo, Brazil;Department of Pathology, A. C. Camargo Cancer Center, São Paulo, Brazil;Department of Statistics, Centro Internacional de Pesquisa e Ensino - Fundação Antônio Prudente, São Paulo, Brazil;PhD/MSc Program, Hospital Sírio-Libanês, São Paulo, Brazil;

关键词: Colorectal cancer;    Angiogenesis;    NOTCH1;    Survival;   

DOI  :  10.1186/s12885-015-1648-4

 received in 2014-12-15, accepted in 2015-09-11,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe development of targeted therapies has undoubtedly broadened therapeutic options for patients with colorectal cancer (CRC). The use of bevacizumab to reduce angiogenesis has been associated with improved clinical outcomes. However, an urgent need for prognostic/predictive biomarkers for anti-angiogenic therapies still exists.MethodsClinical data of 105 CRC patients treated with bevacizumab in conjunction with chemotherapy were analyzed. The expression of vascular endothelial growth factor (VEGF) receptors, NOTCH1 receptor and its ligand DLL4 were determined by immunohistochemistry. Tumor samples were arranged on a tissue microarray. The association between protein expression and clinicopathological characteristics and outcomes was determined.ResultsBevacizumab was administered as a first-line of treatment in 70.5 % of our cases. The median progression-free survival (PFS) was 10.2 months. The median overall survival (OS) of the total cohort was 24.4 months. Bevacizumab, as the first-line of treatment, and the presence of liver metastasis were independently associated with objective response rate. Membrane VEGFR1 and VEGFR3 expressions were associated with the presence of lung metastasis; interestingly, VEGFR3 was associated with less liver metastasis. NOTCH1 expression was associated with lymph node metastasis. There was a trend toward association between improved PFS and lower NOTCH1 expression (p = 0.06). Improved OS was significantly associated with lower NOTCH1 expression (p = 0.01). In a multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status, liver metastasis, histological grade, and NOTCH1 expression were independently associated with OS.ConclusionOur findings illustrated the expression profile of angiogenesis-related proteins and their association with clinicopathological characteristics and outcomes. NOTCH1 expression is a detrimental prognostic factor in metastatic CRC patients treated with chemotherapy plus bevacizumab.

【 授权许可】

CC BY   
© Paiva et al. 2015