title: Blood vessel invasion is a major feature and a factor of poor prognosis in sarcomatoid carcinoma of the lung.
abstract: OBJECTIVE
  Pulmonary sarcomatoid carcinomas (SC) are highly disseminated types of non-small-cell lung carcinoma. Their prognosis is poor. New therapeutic targets are needed to improve disease management.
  
  
  METHODS
  From 1995 to 2013, clinical and survival data from all consecutive patients with surgically treated SC were collected. Pathological and biomarker analyses were performed: TTF1, P63, c-MET and ALK expression (immunohistochemistry), PAS staining, ALK rearrangement (FISH), and EGFR, KRAS, HER2, BRAF, PIK3CA, and MET genes mutations (PCR).
  
  
  RESULTS
  Seventy-seven patients were included. Median age was 61 years (53-69). Histological subtypes were pleomorphic carcinoma (78%), carcinosarcoma (12%), and giant-cell and/or spindle-cell carcinoma (10%). Blood vessel invasion (BVI) was present in 90% of cases. Morphology and immunohistochemistry were indicative of an adenocarcinoma, squamous, and adenosquamous origin in 41.5%, 17% and 11.5%, respectively, 30% remained not-otherwise-specified. KRAS, PIK3CA, EGFR, and MET mutations were found in 31%, 8%, 3%, and 3%, respectively. No tumors had HER2 or BRAF mutations, or ALK rearrangement, whereas 34% had a c-MET positive score. Five-year overall survival (OS) was 29% for the whole population. At multivariate analysis, tumor size <50mm (HR=1.96 [1.04-3.73], p=0.011), no lymph-node metastasis (HR=3.25 [1.68-6.31], p<0.0001), no parietal pleural invasion (HR=1.16 [1.06-1.28], p=0.002), no BVI (HR=1.22 [1.06-1.40], p=0.005), and no squamous component (HR=3.17 [1.48-6.79], p=0.01) were associated with longer OS. Biomarkers did not influence OS.
  
  
  CONCLUSIONS
  Dedifferentiation in NSCLC could lead to SC and an epithelial subtype component could influence outcome. BVI was present in almost all SCs and was an independent factor of poor prognosis.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, Service de Pneumologie, F-75970 Paris, France.
authors.forename: Thibault
authors.initials: T
authors.lastname: Vieira
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, Service d'Anatomie pathologique, F-75970 Paris, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Antoine
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, Service de Pneumologie, F-75970 Paris, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Ruppert
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Fallet
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Duruisseaux
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Giroux Leprieur
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, Plateforme de Génomique des Tumeurs Solides, F-75970 Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Poulot
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rabbe
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France.
authors.forename: Laurene
authors.initials: L
authors.lastname: Sclick
authors.affiliation: Hôpital de Hautepierre, Laboratoire de Biochimie et de biologie moléculaire, F-67098 Strasbourg, France.
authors.forename: Michele
authors.initials: M
authors.lastname: Beau-Faller
authors.affiliation: AP-HP, Hôpital Tenon, Plateforme de Génomique des Tumeurs Solides, F-75970 Paris, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Lacave
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Lavole
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, Service de Pneumologie, F-75970 Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Cadranel
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, Service de Pneumologie, F-75970 Paris, France. Electronic address: marie.wislez@tnn.aphp.fr.
authors.forename: Marie
authors.initials: M
authors.lastname: Wislez
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002296:Carcinosarcoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarker; Blood vessel invasion; Molecular classification; Non-small-cell lung carcinoma; Prognosis; Sarcomatoid carcinoma