title: EGFR and KRAS mutation status in non-small-cell lung cancer occurring in HIV-infected patients.
abstract: Non-small-cell lung cancer (NSCLC) is the most common non-acquired immune deficiency syndrome-related malignancy responsible for death. Mutational status is crucial for choosing treatment of advanced NSCLC, yet no data is available on the frequency of epidermal growth factor receptor (EGFR) and Kirsten ras (KRAS) mutations and their impact on NSCLC in human immunodeficiency virus (HIV)-infected patients (HIV-NSCLC). All consecutive HIV-NSCLC patients diagnosed between June 1996 and August 2013 at two Paris university hospitals were reviewed, with tumor samples analyzed for EGFR and KRAS mutational status. Overall, 63 tumor samples were analyzed out of 73 HIV-NSCLC cases, with 63% of advanced NSCLC. There were 60 non-squamous and nine squamous cell carcinomas, with EGFR and KRAS mutations identified in two (3.3%) and seven (11.5%) tumors, respectively. The proportion of KRAS mutations was 29% if solely the more sensitive molecular techniques were considered. The two patients with advanced adenocarcinoma harboring EGFR mutations exhibited lasting partial response to EGFR-tyrosine kinase inhibitors. Overall survival for patients with advanced NSCLC were >30 months for those with EGFR mutations, <3 months for KRAS mutations (n=2), and the median was 9 months [4.1-14.3] for wild-type (n=34). In multivariate analysis, KRAS mutation and CD4<200 cells/μL were associated with poor prognosis (hazard ratio (HR): 24 [4.1-140.2], p=0.0004; HR: 3.1 [1.3-7.5], p=0.01, respectively). EGFR mutation must be investigated in HIV-NSCLC cases due to its predictive and prognostic impact, whereas KRAS mutation is of poor prognostic value. Clinicians should search for drugs dedicated to this target population.
authors.affiliation: Service de Pneumologie, AP-HP, Hôpital Tenon, Paris, France.
authors.forename: Perrine
authors.initials: P
authors.lastname: Créquit
authors.affiliation: Service de Pneumologie, AP-HP, Hôpital Tenon, Paris, France; Sorbonne Universités, UPMC Univ. Paris 06, GRC-04, Théranoscan, Paris, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Ruppert
authors.affiliation: Service de Pneumologie, AP-HP, Hôpital Tenon, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rozensztajn
authors.affiliation: Service de Pneumologie, AP-HP, Hôpital Tenon, Paris, France; Sorbonne Universités, UPMC Univ. Paris 06, GRC-04, Théranoscan, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gounant
authors.affiliation: Service de Pneumologie, AP-HP, Hôpital Tenon, Paris, France; Sorbonne Universités, UPMC Univ. Paris 06, GRC-04, Théranoscan, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Vieira
authors.affiliation: Sorbonne Universités, UPMC Univ. Paris 06, GRC-04, Théranoscan, Paris, France; Plateforme de Génomique des Tumeurs solides et Cytologie pathologiques, AP-HP, Hôpital Tenon, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Poulot
authors.affiliation: Sorbonne Universités, UPMC Univ. Paris 06, GRC-04, Théranoscan, Paris, France; Service d'Anatomie pathologique, AP-HP, Hôpital Tenon, Paris, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Antoine
authors.affiliation: Service de Pneumologie, Centre Hospitalier Intercommunal, Créteil, France.
authors.forename: Christos
authors.initials: C
authors.lastname: Chouaid
authors.affiliation: Service de Pneumologie, AP-HP, Hôpital Tenon, Paris, France; Sorbonne Universités, UPMC Univ. Paris 06, GRC-04, Théranoscan, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Wislez
authors.affiliation: Service de Pneumologie, AP-HP, Hôpital Tenon, Paris, France; Sorbonne Universités, UPMC Univ. Paris 06, GRC-04, Théranoscan, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Cadranel
authors.affiliation: Service de Pneumologie, AP-HP, Hôpital Tenon, Paris, France; Sorbonne Universités, UPMC Univ. Paris 06, GRC-04, Théranoscan, Paris, France. Electronic address: armelle.lavole@tnn.aphp.fr.
authors.forename: Armelle
authors.initials: A
authors.lastname: Lavole
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000821:virology*; D004252:DNA Mutational Analysis / Q000379:methods; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Epidermal growth factor receptor (EGFR) mutation; Human immunodeficiency virus (HIV); Kirsten Ras (KRAS) mutation; Non-small-cell lung cancer (NSCLC)