title: Prognostic tissue biomarker exploration for patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor receptor tyrosine kinase inhibitors.
abstract: In metastatic renal cell carcinoma (mRCC), the prognostic role of several tumor tissue biomarkers has been evaluated, but the results were controversial. This study aims to verify the prognostic importance of selected tumor tissue biomarkers in patients with mRCC. The clinicopathological features, immunohistochemical staining and scoring for select tissue biomarkers, treatment, and outcome of patients with mRCC treated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) between July 2006 and March 2011 at Asan Medical Center in Seoul, South Korea, were reviewed. In total, 123 patients met the inclusion criteria. Most patients had clear-cell carcinoma (107 patients, 87.0 %). First-line VEGFR TKIs were sunitinib (97 patients, 78.9 %), sorafenib (23 patients, 18.7 %), and pazopanib (3 patients, 2.4 %). With a median follow-up period of 60.0 months (95 % confidence interval (CI), 56.3-63.6), median overall survival (OS) and progression-free survival (PFS) were 25.6 months (95 % CI, 19.2-32.0) and 12.2 months (95 % CI, 8.1-16.3), respectively. In the multivariable analysis for OS, carbonic anhydrase IX (CAIX; 47.5 % or less vs. more than 47.5 %, p = 0.014), sarcomatoid change (40 % or less vs. more than 40 %, p < 0.001), tumor necrosis (20 % or less vs. more than 20 %, p = 0.006), and Heng's risk group (good vs. intermediate vs. poor, p = 0.011) were identified as independent prognostic factors. In the multivariable analysis for PFS, CAIX (p < 0.001), phosphatase and tensin homolog (PTEN; 45 % or less vs. more than 45 %, p = 0.004), sarcomatoid change (p = 0.002), and tumor necrosis (p = 0.001) were identified as independent factors affecting PFS. CAIX and PTEN had prognostic importance for mRCC patients receiving first-line VEGFR TKI. Future validation and mechanistic studies are required.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Republic of Korea.|Department of Internal Medicine, Gachon University Gil Medical Centre, 1198, Guwol-Dong, Namdong-Gu, Incheon, 405-760, Republic of Korea.
authors.forename: Inkeun
authors.initials: I
authors.lastname: Park
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Yong Mee
authors.initials: YM
authors.lastname: Cho
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Republic of Korea. jaelyun@amc.seoul.kr.
authors.forename: Jae-Lyun
authors.initials: JL
authors.lastname: Lee
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Republic of Korea.
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Republic of Korea.
authors.forename: Dae-Ho
authors.initials: DH
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D000071231:Carbonic Anhydrase IX / Q000096:biosynthesis / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics*; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D000077157:Sorafenib; D000077210:Sunitinib; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D040281:Vascular Endothelial Growth Factor Receptor-1; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000071231:Carbonic Anhydrase IX; D000077210:Sunitinib
keywords: Biomarker; Carbonic anhydrase IX; PTEN; Prognosis; Renal cell carcinoma