title: CD34 immunostaining enhances a distinct pattern of intratumor angiogenesis with prognostic implications in clear cell renal cell carcinoma.
abstract: Clear cell renal cell carcinoma is an aggressive neoplasm related to VHL gene inactivation. The molecular events derived from this initial alteration lead to a permanent intracellular pseudo-hypoxic status that stimulates vascular proliferation. The resulting increased intratumor angiogenesis is the target of most modern therapies. Although intratumor angiogenesis has received full attention in the last years, few studies have focused on its potential importance from a strict morphological approach. Intratumor angiogenesis has been analyzed in a retrospective series of clear cell renal cell carcinomas (n = 208) with long-term follow-up (n = 177). Two different patterns of angiogenesis have been highlighted with CD34 at the front of tumor invasion, termed continuous and discontinuous, respectively. The continuous pattern of angiogenesis showed a complete microvascular network surrounding totally tumor nests. Conversely, the discontinuous pattern displayed an incomplete network around tumor nests. The continuous pattern was associated to shorter 5-year (p = 0.00064, hazard ratio = 2.8) and 15-year (p = 0.014, hazard ratio = 1.7) survivals. Cox regression multivariate analysis also showed that the continuous pattern (p = 0.016373) remains a significant variable when considered together with grade (p = 0.001755) and stage (p = 0.000952). These findings support the notion that a continuous CD34+pattern of intratumor angiogenesis may be useful for pathologists in predicting tumor behavior in clear cell renal cell carcinomas.
authors.affiliation: Department of Pathology, Cruces University Hospital, University of the Basque Country (UPV/EHU), Barakaldo, Bizkaia, Spain.|Biomarkers in Cancer Unit, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.
authors.forename: José I
authors.initials: JI
authors.lastname: López
authors.affiliation: Quantitative Biomedicine Unit, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.
authors.forename: Asier
authors.initials: A
authors.lastname: Erramuzpe
authors.affiliation: Department of Pathology, Complejo Hospitalario B de Navarra, Pamplona, Navarra, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Guarch
authors.affiliation: Quantitative Biomedicine Unit, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.|Ikerbasque, Basque Foundation for Science, Bilbao, Bizkaia, Spain.|Department of Cell Biology and Histology, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Cortés
authors.affiliation: Biomarkers in Cancer Unit, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.|Ikerbasque, Basque Foundation for Science, Bilbao, Bizkaia, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Pulido
authors.affiliation: Department of Urology, Cruces University Hospital, University of the Basque Country (UPV/EHU), Barakaldo, Bizkaia, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Llarena
authors.affiliation: Department of Urology, Hospital de Getafe, Universidad Europea de Madrid, Madrid, Spain.
authors.forename: Javier C
authors.initials: JC
authors.lastname: Angulo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008853:Microscopy; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D010338:Pathology, Clinical / Q000379:methods*; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D018952:Antigens, CD34
keywords: CD34; Clear cell renal cell carcinoma; angiogenesis; prognosis; survival