caa a22 4500 445334576 CHVBK 20180317142750.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1245/s10434-011-1775-3 doi (NATIONALLICENCE)springer-10.1245/s10434-011-1775-3 Clinically Relevant Biomarkers to Select Patients for Targeted Inhibitor Therapy after Resection of Hepatocellular Carcinoma [Elektronische Daten] [Sameer Patel, Peter Kneuertz, Maria Delgado, David Kooby, Charles Staley III, Bassel El-Rayes, John Kauh, Juan Sarmiento, Steven Hanish, Cynthia Cohen, Alton Farris III, Shishir Maithel] Background: Hepatocellular carcinoma (HCC) is a vascular tumor that proliferates through angiogenic pathways mediated, in part, by vascular endothelial growth factor receptor 2 (VEGFR2), and platelet-derived growth factor receptor (PDGFR) α and β. We hypothesized that overexpression of these proteins is associated with decreased survival after resection. Methods: A total of 57 patients, with available tissue for analysis, who underwent liver resection for HCC between August 2000 and March 2008 at a single institution were identified from a prospectively maintained database. Tumor specimens were assessed with immunohistochemistry for VEGFR2, PDGFR-α, and PDGFR-β expression and were graded by an experienced pathologist. Primary outcome was overall survival (OS). Results: Median patient age was 64years; 65% (n=37) were male. Median follow-up was 24.5months, and median OS was 25.5months. Median tumor size and number were 7cm and 1, respectively. Macro and microvascular invasion was present in 9% (n=5) and 42% (n=24) of patients, respectively. Seventy-five percent of patients had tumors exceeding Milan criteria. 9% had positive resection margins. Thirty-five percent of patients had cirrhosis and the median nonadjusted Model for End-Stage Liver Disease (MELD) score was 7.5. Tumors exhibited differential expression of VEGFR2 (low: 79%, high: 21%), PDGFR-α (low: 93%, high: 7%), and PDGFR-β (low: 96%, high: 4%). After excluding all 30-day deaths (n=7), high PDGFR-α and PDGFR-β expression were independently associated with decreased OS (8.7 vs 29.1months, P=0.01; 2.8 vs 28.8months, P<0.001; respectively). High VEGFR2 expression displayed a trend toward decreased OS (20.8 vs 27.5months, P=0.2). When adjusted for tumor burden, vascular invasion, margin status, and MELD score on independent multivariate analyses, both PDGFR-α and -β high expression were independently associated with decreased survival. Conclusions: High expression of PDGFR-α and PDGFR-β may be independently associated with decreased OS irrespective of margin status, MELD score, and tumor extent. This finding may help to select patients who would benefit from targeted inhibitor therapy in the adjuvant setting. Society of Surgical Oncology, 2011 Patel Sameer Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut Kneuertz Peter Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut Delgado Maria Department of Pathology, Emory University, Atlanta, GA, USA aut Kooby David Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut Staley III Charles Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut El-Rayes Bassel Department of Medicine, Division of Hematology/Oncology, Emory University, Atlanta, GA, USA aut Kauh John Department of Medicine, Division of Hematology/Oncology, Emory University, Atlanta, GA, USA aut Sarmiento Juan Department of Surgery, Division of General Surgery, Emory University, Atlanta, GA, USA aut Hanish Steven Department of Surgery, Division of Transplantation, Emory University, Atlanta, GA, USA aut Cohen Cynthia Department of Pathology, Emory University, Atlanta, GA, USA aut Farris III Alton Department of Pathology, Emory University, Atlanta, GA, USA aut Maithel Shishir Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut Annals of Surgical Oncology Springer-Verlag 18/12(2011-11-01), 3384-3390 1068-9265 18:12<3384 2011 18 10434 https://doi.org/10.1245/s10434-011-1775-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1245/s10434-011-1775-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Patel Sameer Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Kneuertz Peter Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Delgado Maria Department of Pathology, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Kooby David Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Staley III Charles Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- El-Rayes Bassel Department of Medicine, Division of Hematology/Oncology, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Kauh John Department of Medicine, Division of Hematology/Oncology, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Sarmiento Juan Department of Surgery, Division of General Surgery, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Hanish Steven Department of Surgery, Division of Transplantation, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Cohen Cynthia Department of Pathology, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Farris III Alton Department of Pathology, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Maithel Shishir Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA aut NATIONALLICENCE 773 0- Annals of Surgical Oncology Springer-Verlag 18/12(2011-11-01), 3384-3390 1068-9265 18:12<3384 2011 18 10434 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer