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

Autor(es)

Paiva, Jr., Tadeu Ferreira ^[1] ; Fonseca de Jesus, Victor Hugo ^[1] ; Marques, Raul Amorim ^[1] ; Balieiro Anastacio da Costa, Alexandre Andre ^[1] ; de Macedo, Mariana Petaccia ^[2] ; Peresi, Patricia Maria ^[2] ; Damascena, Aline ^[3] ; Rossi, Benedito Mauro ^[4] ; Begnami, Maria Dirlei ^[2] ; Cordeiro de Lima, Vladmir Claudio ^{[1, 5]}

Afiliação do(s) autor(es)

^[1] AC Camargo Canc Ctr, Dept Med Oncol, Sao Paulo - Brazil

^[2] AC Camargo Canc Ctr, Dept Pathol, Sao Paulo - Brazil

^[3] Fundacao Antonio Prudente, Ctr Int Pesquisa & Ensino, Dept Stat, Sao Paulo - Brazil

^[4] Hosp Sirio Libanes, PhD MSc Program, Sao Paulo - Brazil

^[5] Dept Clin Oncol, BR-01509900 Sao Paulo, ZC - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BMC CANCER; v. 15, SEP 22 2015.
• Citações Web of Science: 16

Resumo

Background: The 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. Methods: Clinical 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. Results: Bevacizumab 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. Conclusion: Our 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. (AU)

• Processo FAPESP: 10/07858-2 - Correlação entre a expressão de integrinas e de proteínas envolvidas em neoangiogênese em tumores colorretais e resposta ao tratamento com bevacizumabe
• Beneficiário: Vladmir Cláudio Cordeiro de Lima
• Modalidade de apoio: Auxílio à Pesquisa - Regular