title: KRAS-mutation incidence and prognostic value are metastatic site-specific in lung adenocarcinoma: poor prognosis in patients with KRAS mutation and bone metastasis.
abstract: Current guidelines lack comprehensive information on the metastatic site-specific role of KRAS mutation in lung adenocarcinoma (LADC). We investigated the effect of KRAS mutation on overall survival (OS) in this setting. In our retrospective study, 500 consecutive Caucasian metastatic LADC patients with known KRAS mutational status were analyzed after excluding 32 patients with EGFR mutations. KRAS mutation incidence was 28.6%. The most frequent metastatic sites were lung (45.6%), bone (26.2%), adrenal gland (17.4%), brain (16.8%), pleura (15.6%) and liver (11%). Patients with intrapulmonary metastasis had significantly increased KRAS mutation frequency compared to those with extrapulmonary metastases (35% vs 26.5%, p = 0.0125). In contrast, pleural dissemination and liver involvement were associated with significantly decreased KRAS mutation incidence (vs all other metastatic sites; 17% (p < 0.001) and 16% (p = 0.02) vs 33%, respectively). Strikingly, we found a significant prognostic effect of KRAS status only in the bone metastatic subcohort (KRAS-wild-type vs KRAS-mutant; median OS 9.7 v 3.7 months; HR, 0.49; 95% CI, 0.31 to 0.79; p  = 0.003). Our study suggests that KRAS mutation frequency in LADC patients shows a metastatic site dependent variation and, moreover, that the presence of KRAS mutation is associated with significantly worse outcome in bone metastatic cases.
authors.affiliation: National Koranyi Institute of Pulmonology, Budapest, Hungary.|Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Lohinai
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klikovits
authors.affiliation: National Koranyi Institute of Pulmonology, Budapest, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Moldvay
authors.affiliation: National Koranyi Institute of Pulmonology, Budapest, Hungary.
authors.forename: Gyula
authors.initials: G
authors.lastname: Ostoros
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Raso
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.|Molecular Oncology Research Group, Hungarian Academy of Sciences-Semmelweis University, Budapest, Hungary.
authors.forename: Jozsef
authors.initials: J
authors.lastname: Timar
authors.affiliation: Department of Pulmonology, Semmelweis University, Budapest, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Fabian
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: Ilona
authors.initials: I
authors.lastname: Kovalszky
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Kenessey
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria.|Department of Thoracic Surgery, Ruhrlandklinik Essen, University Hospital of University Duisburg-Essen, Essen, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Aigner
authors.affiliation: Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Budapest, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Renyi-Vamos
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.affiliation: National Koranyi Institute of Pulmonology, Budapest, Hungary.|Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria.|Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Budapest, Hungary.|Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Balazs
authors.initials: B
authors.lastname: Dome
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria.|Molecular Oncology Research Group, Hungarian Academy of Sciences-Semmelweis University, Budapest, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Hegedus