title: Prognostic and Therapeutic Markers in Chordomas: A Study   of 287 Tumors.
abstract: Chordomas are slow-growing malignant neoplasms. Determination of histopathologic prognostic factors using a large cohort study has been limited by their low incidence. In this retrospective study, we investigated the clinical, histopathologic, and immunohistochemical prognostic factors in 287 chordomas from 111 patients assessed by central pathologic review. Expression patterns of a variety of markers, including vascular endothelial growth factor (VEGF), mTOR pathway, c-kit, HER2, epidermal growth factor receptor (EGFR) and STAT3, and KRAS, BRAF, EGFR, and PIK3CA mutations were analyzed. On univariate analysis, the results confirm surgery as the best treatment, as judged by patient progression-free survival (PFS) and overall survival (OS). Proton therapy, the presence of a dedifferentiated component, mitotic figures, and Ki67 and p53 labeling indices correlated with PFS . Necrosis and apoptosis correlated with OS. Based on these findings, we propose a histopathologic grading system that correlates with PFS and OS. On multivariate analysis, extent of resection, tumor grade, and proton therapy were independent prognostic factors of PFS; extent of resection, tumor location, and grade were independent prognostic factors of OS. Based on the expression of EGFR, pSTAT3, VEGF, and mTOR pathway proteins, (in 85.9%, 79.1%, 85.7%, and 46% of chordomas, respectively), and 2 new mutations in the PIK3CA gene, we also provide evidence for potential therapeutic targets.
authors.forename: Arnault
authors.initials: A
authors.lastname: Tauziéde-Espariat
authors.forename: Damien
authors.initials: D
authors.lastname: Bresson
authors.forename: Marc
authors.initials: M
authors.lastname: Polivka
authors.forename: Schahrazed
authors.initials: S
authors.lastname: Bouazza
authors.forename: François
authors.initials: F
authors.lastname: Labrousse
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Pretet
authors.forename: Fabrice
authors.initials: F
authors.lastname: Projetti
authors.forename: Philippe
authors.initials: P
authors.lastname: Herman
authors.forename: Henri
authors.initials: H
authors.lastname: Salle
authors.forename: Franck
authors.initials: F
authors.lastname: Monnien
authors.forename: Séverine
authors.initials: S
authors.lastname: Valmary-Degano
authors.forename: Annie
authors.initials: A
authors.lastname: Laquerrière
authors.forename: Marc
authors.initials: M
authors.lastname: Pocard
authors.forename: Loïc
authors.initials: L
authors.lastname: Chaigneau
authors.forename: Nicolas
authors.initials: N
authors.lastname: Isambert
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Aubriot-Lorton
authors.forename: Loïc
authors.initials: L
authors.lastname: Feuvret
authors.forename: Bernard
authors.initials: B
authors.lastname: George
authors.forename: Sébastien
authors.initials: S
authors.lastname: Froelich
authors.forename: Homa
authors.initials: H
authors.lastname: Adle-Biassette
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D002817:Chordoma / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D060787:Neoplasm Grading; D018365:Neoplasm, Residual / Q000473:pathology; D011379:Prognosis; D011522:Protons; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D011522:Protons