title: Setting up a wide panel of patient-derived tumor xenografts of non-small cell lung cancer by improving the preanalytical steps.
abstract: With the ongoing need to improve therapy for non-small cell lung cancer (NSCLC) there has been increasing interest in developing reliable preclinical models to test novel therapeutics. Patient-derived tumor xenografts (PDX) are considered to be interesting candidates. However, the establishment of such model systems requires highly specialized research facilities and introduces logistic challenges. We aimed to establish an extensive well-characterized panel of NSCLC xenograft models in the context of a long-distance research network after careful control of the preanalytical steps. One hundred fresh surgically resected NSCLC specimens were shipped in survival medium at room temperature from a hospital-integrated biobank to animal facilities. Within 24 h post-surgery, tumor fragments were subcutaneously xenografted into immunodeficient mice. PDX characterization was performed by histopathological, immunohistochemical, aCGH and next-generation sequencing approaches. For this model system, the tumor take rate was 35%, with higher rates for squamous carcinoma (60%) than for adenocarcinoma (13%). Patients for whom PDX tumors were obtained had a significantly shorter disease-free survival (DFS) compared to patients for whom no PDX tumors (P = 0.039) were obtained. We established a large panel of PDX NSCLC models with a high frequency of mutations (29%) in EGFR, KRAS, NRAS, MEK1, BRAF, PTEN, and PI3KCA genes and with gene amplification (20%) of c-MET and FGFR1. This new patient-derived NSCLC xenograft collection, established regardless of the considerable time required and the distance between the clinic and the animal facilities, recapitulated the histopathology and molecular diversity of NSCLC and provides stable and reliable preclinical models for human lung cancer research.
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Louis Pasteur Hospital, Nice, France; IRCAN Team 3, Inserm U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice, France; Faculty of Medicine, University of Nice Sophia-Antipolis, Nice, France; Hospital Related Biobank BB-0033-00025, Louis Pasteur Hospital, Nice, France.
authors.forename: Marius
authors.initials: M
authors.lastname: Ilie
authors.forename: Manoel
authors.initials: M
authors.lastname: Nunes
authors.forename: Lydia
authors.initials: L
authors.lastname: Blot
authors.forename: Véronique
authors.initials: V
authors.lastname: Hofman
authors.forename: Elodie
authors.initials: E
authors.lastname: Long-Mira
authors.forename: Catherine
authors.initials: C
authors.lastname: Butori
authors.forename: Eric
authors.initials: E
authors.lastname: Selva
authors.forename: Ana
authors.initials: A
authors.lastname: Merino-Trigo
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vénissac
authors.forename: Jérôme
authors.initials: J
authors.lastname: Mouroux
authors.forename: Patricia
authors.initials: P
authors.lastname: Vrignaud
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D017422:Sequence Analysis, DNA; D016019:Survival Analysis
keywords: Molecular pathology; NSCLC; PDX; preanalytical