title: Tissue Biomarkers in Predicting Response to Sunitinib Treatment of Metastatic Renal Cell Carcinoma.
abstract: OBJECTIVE
  To identify tissue biomarkers that are predictive of the therapeutic effect of sunitinib in treatment of metastatic clear cell renal cell carcinoma (mCRCC).
  
  
  METHODS
  Our study included 39 patients with mCRCC treated with sunitinib. Patients were stratified into two groups based on their response to sunitinib treatment: non-responders (progression), and responders (stable disease, regression). The effect of treatment was measured by comparing imaging studies before the initiation treatment with those performed at between 3rd and 7th months of treatment, depending on the patient. Histological samples of tumor tissue and healthy renal parenchyma, acquired during surgery of the primary tumor, were examined with immunohistochemistry to detect tissue targets involved in the signaling pathways of tumor growth and neoangiogenesis. We selected mammalian target of rapamycine, p53, vascular endothelial growth factor, hypoxia-inducible factor 1 and 2 and carbonic anhydrase IX. We compared the average levels of biomarker expression in both, tumor tissue, as well as in healthy renal parenchyma. Results were evaluated using the Student's t-test.
  
  
  RESULTS
  For responders, statistically significant differences in marker expression in tumor tissue versus healthy parenchyma were found for mTOR (4%/16.7%; p=0.01031), p53 (4%/12.7%; p=0.042019), VEGF (62.7%/45%; p=0.019836) and CAIX (45%/15.33%; p=0.001624). A further significant difference was found in the frequency of high expression (more than 60%) between tumor tissue and healthy parenchyma in VEGF (65%/35%; p=0.026487) and CAIX (42%/8%; p=0.003328). CAIX was expressed at high levels in the tumor tissue in both evaluated groups.
  
  
  CONCLUSIONS
  A significantly higher expression of VEGF in CRCC in comparison to healthy parenchyma can predict a better response to sunitinib.
authors.affiliation: Department of Urology, Faculty Hospital in Pilsen, Pilsen, Czech Republic travniceki@fnplzen.cz.
authors.forename: Ivan
authors.initials: I
authors.lastname: Trávníček
authors.affiliation: Department of Pathology, Faculty Hospital in Pilsen, Pilsen, Czech Republic.
authors.forename: Jindřich
authors.initials: J
authors.lastname: Branžovský
authors.affiliation: Department of Urology, Faculty Hospital in Pilsen, Pilsen, Czech Republic.
authors.forename: Kristýna
authors.initials: K
authors.lastname: Kalusová
authors.affiliation: Department of Pathology, Faculty Hospital in Pilsen, Pilsen, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Hes
authors.affiliation: Department of Oncology and Radiotherapy, Faculty Hospital in Pilsen, Pilsen, Czech Republic.
authors.forename: Luboš
authors.initials: L
authors.lastname: Holubec
authors.affiliation: Department of Pathology, Faculty Hospital in Pilsen, Pilsen, Czech Republic.
authors.forename: Kevin Bauleth
authors.initials: KB
authors.lastname: Pele
authors.affiliation: Department of Urology, Faculty Hospital in Pilsen, Pilsen, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Ürge
authors.affiliation: Department of Urology, Faculty Hospital in Pilsen, Pilsen, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Hora
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007211:Indoles / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D015996:Survival Rate; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Metastatic renal carcinoma; biomarkers; immunohistochemistry; prediction; targeted-therapy