K-ras gene mutations: an unfavorable prognostic marker in stage I lung adenocarcinoma

E. M. Silini, F. Bosi, E. Solcia, R. Fiocca, N. S. Pellegata, G. N. Ranzani, G. Volpato, A. Romano, S. Nazari, C. Tinelli

Research output: Contribution to journalArticle

Abstract

Activation of K-ras gene by point mutations, a common finding in lung adenocarcinomas, has been suggested to decrease patient survival. We investigated 109 lung adenocarcinomas, mostly small, peripheral, stage I tumours (81/109) for presence of K-ras gene mutations at codons 12 and 13. Mutations were detected by denaturing gradient gel electrophoresis analysis of specific sequences amplified by polymerase chain reaction from DNA extracted from archival pathological material. Thirty-three of 109 (30.3%) tumours showed mutations at codon 12 (28/33, 84.8%) or 13 (5/33, 15.2%) of the gene. Mutations and type of nucleotide substitutions were differently distributed among cytological subtypes, being more prevalent among less differentiated (G2 and G3) tumours and among bronchial than bronchiolo-alveolar type adenocarcinomas. Survival analysis showed an adverse effect of K-ras mutation on survival, restricted to stage I tumours. Median survival for 81 stage I patients was 30 months for non-mutated tumours versus 20 months for mutated tumours (p=0.016). Multivariate analysis showed that age of patient (p=0.001) and K-ras mutation status (p=0.04) were the only independent factors influencing survival significantly. These data strengthen the hypothesis that K-ras gene mutations may be useful in identifying a subgroup of patients with poor outcome.

Original languageEnglish
Pages (from-to)367-373
Number of pages7
JournalVirchows Archiv
Volume424
Issue number4
DOIs
Publication statusPublished - May 1994

Keywords

  • K-ras gene
  • Lung adenocarcinoma
  • Point mutation
  • Survival analysis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Silini, E. M., Bosi, F., Solcia, E., Fiocca, R., Pellegata, N. S., Ranzani, G. N., Volpato, G., Romano, A., Nazari, S., & Tinelli, C. (1994). K-ras gene mutations: an unfavorable prognostic marker in stage I lung adenocarcinoma. Virchows Archiv, 424(4), 367-373. https://doi.org/10.1007/BF00190558