1186P - Gene amplification of actn4 in lung cancer: a novel prognostic indicator for stage I adenocarcinoma of the lung

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Non-Small-Cell Lung Cancer, Early Stage
Translational Research
Presenter Kazufumi Honda
Authors K. Honda1, R. Noro2, N. Miura1, K. Tsuta3, G. Ishii4, H. Tsuda3, A. Gennma2, H. Asamura5, K. Nagai6, T. Yamada1
  • 1Division Of Chemotherapy And Clinical Research, National Cancer Center Research Institute, 104-0045 - Tokyo/JP
  • 2Department Of Internal Medicine, Division Of Pulmonary Medicine, Infectious Diseases And Oncology, Nippon Medical School, Tokyo/JP
  • 3Pathology And Clinical Laboratory Division, National Cancer Center Hospital, Tokyo/JP
  • 4Department Of Pathology, National Cancer Center Hospital East, Kashiwa/JP
  • 5Division Of Thoracic Surgery, National Cancer Center Hospital, Tokyo/JP
  • 6Department Of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa/JP

Abstract

Background

Even if detected at an early stage, a substantial number of lung cancers relapse after surgery. Patients with such tumors are likely to benefit from adjuvant therapy, but methods for identifying such patients have yet to be established.

Methods

We retrospectively analyzed multiple cohorts totaling 1744 patients who underwent resection of lung adenocarcinoma. Expression of actinin-4 protein in tumors was evaluated immunohistochemically, and copy numbers of the actinin-4 (ACTN4) gene were determined by fluorescence in situ hybridization.

Results

Amplification of the ACTN4 gene correlated significantly with smoking history (P = 0.02), pathological stage (P = 0.002), and histological differentiation (P < 0.001, chi-squared test). Overall survival was significantly worse for patients with stage I lung adenocarcinoma harboring ACTN4 gene amplification than for those with tumors showing no such gene amplification (P < 0.001, log-rank test). Multivariate analysis revealed ACTN4 gene amplification in stage I lung adenocarcinoma as an independent factor associated with higher risk of death (hazard ratio, 6.78; 95% confidence interval, 2.59-17.7; P < 0.001, Cox regression analysis). The 5-year survival rate of patients with stage I lung adenocarcinoma showing increased actinin-4 protein expression and ACTN4 gene amplification was 58%, compared to 87% for patients with tumors lacking gene amplification and 95% for patients with tumors lacking actinin-4 protein expression. The former group showed significantly worse overall survival than either of the latter (P < 0.001).

Conclusions

Amplification of the actinin-4 gene defines a subset of stage I lung adenocarcinoma with distinctly poor outcomes.

Disclosure

All authors have declared no conflicts of interest.