title: High pKDR immunohistochemical expression is an unfavourable prognostic biomarker in patients with advanced colorectal cancer treated with chemotherapy plus bevacizumab.
abstract: OBJECTIVE
  To analyse the prognostic role of the immunohistochemical expression of pKDR in patients with advanced colorectal cancer treated with oxaliplatin and fluoropyrimidines combination chemotherapy with or without bevacizumab.
  
  
  METHODS
  Retrospective multicentre study, carried out at four hospitals in the Valencian Community (Spain). Patients evolution was compared based on the immunohistochemical expression of pKDR, classified using 4 categories: 0 (undetectable), 1 (mild), 2 (moderate) and 3 (high intensity). Patients were divided into two groups for the analysis: group 1 with low expression (0-1) vs. group 2 with high expression (2-3).
  
  
  RESULTS
  Histological samples for the pKDR analysis were available for 84 of the 112 patients selected. Seven (8.3 %) had undetectable or mild expression of pKDR (Group 1) and 77 (91.7 %) showed moderate or high expression of pKDR (Group 2). Response rate in Group 1 was 100 % compared to 54.2 % in Group 2 (p = 0.019). Progression-free survival (PFS) (15 vs. 12 months, p = 0.4) and overall survival (OS) (28 vs. 22 months, p = 0.09) were numerically but not significantly higher in patients from Group 1 vs. Group 2. Patients from Group 2 who received bevacizumab presented a significantly higher PFS (13 vs. 11, p = 0.015) and a numerically higher OS (23 vs. 17 months, p = 0.27) than those treated exclusively with chemotherapy.
  
  
  CONCLUSIONS
  Our results suggest that the absence or low expression of pKDR is associated with a better prognostic profile in patients with advanced colorectal cancer treated with chemotherapy and bevacizumab. Patients with a high pKDR expression benefit from the combination of chemotherapy with bevacizumab.
authors: Medical Oncology Department, Hospital Arnau de Vilanova (Arnau de Vilanova Hospital), c/San Clemente no. 12, 46015, Valencia, Spain. javiergardenoguera1@gmail.com.
authors: J
authors: J
authors: Garde-Noguera
authors: Medical Oncology Department, Hospital de Sagunto, Valencia, Spain.
authors: M
authors: M
authors: Gil-Raga
authors: Anatomic Pathology Department, Hospital MarinaSalud de Denia, Alicante, Spain.
authors: E
authors: E
authors: Evgenyeva
authors: Anatomic Pathology, Hospital General Universitario de Valencia, Valencia, Spain.
authors: J A
authors: JA
authors: García
authors: Medical Oncology Department, Hospital Arnau de Vilanova (Arnau de Vilanova Hospital), c/San Clemente no. 12, 46015, Valencia, Spain.
authors: A
authors: A
authors: Llombart-Cussac
authors: Medical Oncology Department, Hospital General Universitario de Valencia, Valencia, Spain.|Valencia University, Valencia, Spain.
authors: C
authors: C
authors: Camps-Herrero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010766:Phosphorylation; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D005472:Fluorouracil
keywords: Bevacizumab; Biomarkers; Colorectal cancer; pKDR