AUTHOR=Ouzaid Idir , Kammerer-Jacquet Solène Florence , Khene Zineddine , Ravaud Alain , Patard Jean-Jacques , Bensalah Karim , Rioux-Leclercq Nathalie 

TITLE=Exploring Biological Predictive Factors of Progression After Surgery in High-Risk Renal Cell Carcinoma: Results From the French Cohort of the Randomized S-TRAC Trial Patients

JOURNAL=Frontiers in Surgery

VOLUME=7

YEAR=2020

URL=https://www.frontiersin.org/journals/surgery/articles/10.3389/fsurg.2020.00026

DOI=10.3389/fsurg.2020.00026

ISSN=2296-875X

ABSTRACT=<p><bold>Objective:</bold> We aimed to explore biological predictive factors of progression after surgery in nonmetastatic renal cell carcinoma (RCC) using the collected tumors in the French cohort of the randomized S-TRAC trial patients.</p><p><bold>Patients and Methods:</bold> We analyzed the tumors of the French cohort of STRAC that included 44 cases of clear cell RCC (ccRCC) that were collected from six centers. The main objective was to explore biological predictive factors of progression (defined as PFS) to sunitinib. Broad-spectrum analysis including immunohistochemistry, fluorescent <italic>in situ</italic> hybridization (FISH), comparative genomic hybridization (CGH) array, and transcriptomic analyses were performed on the tumors.</p><p><bold>Results:</bold>Analysis of vascular density showed type 1 vascular stroma corresponding to high vascular density was associated with progression (<italic>p</italic> &lt; 0.034). Loss of poly bromo-1 expression showed a distinct profile: a highly histopathological aggressive tumor with a marked angiogenic profile (vascular endothelial growth factor overexpression and immature vascular stroma type 2), no PD1 or PDL1 expression, and wild-type (WT) status of the <italic>VHL</italic> gene. There were 27 chromosome regions gained in patients with progression (on chromosomes 7 and 16, and to a lesser extent 8, 12, 17, 17, 19, 20 corresponding to 605 associated genes) and 10 regions lost in these same patients on chromosomes 8 and 9, and to a lesser extent 2 and 21 corresponding to 25 associated genes.</p><p><bold>Conclusion:</bold>We found that an angiogenic phenotype defined by a high vascular density with a vascular type 2 stroma was a predictive factor of sunitinib resistance. Regardless of adjuvant treatment, chromosomal gains and losses and genomic alterations including <italic>PBRM1</italic> loss were associated with worse outcomes.</p><p><bold>Clinical Trial Registration</bold>: ClinicalTrials.gov number, NCT00375674.</p>