1174P - Diagnostic and prognostic significance of the alternatively spliced actn4 variant in high-grade neuroendocrine pulmonary tumours

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Neuroendocrine Cancers
Translational Research
Presenter Akihiko Miyanaga
Authors A. Miyanaga1, K. Honda2, K. Tsuta2, M. Masuda2, H. Tsuda3, H. Asamura4, A. Gemma5, T. Yamada2
  • 1Division Of Pulmonary Medicine, Infectious, National Cancer Center Research Institute, 104-0045 - Tokyo/JP
  • 2Division Of Chemotherapy And Clinical Research, National Cancer Center Research Institute, 104-0045 - Tokyo/JP
  • 3Pathology And Clinical Laboratory Division, National Cancer Center Hospital, Tokyo/JP
  • 4Division Of Thoracic Surgery, National Cancer Center Hospital, Tokyo/JP
  • 5Nippon Medical School, Tokyo/JP

Abstract

Background

High-grade neuroendocrine tumours (HGNTs) of the lung manifest a wide spectrum of clinical behaviour, but no method of predicting their outcome has been established.

Materials and methods

We newly established a monoclonal antibody specifically recognizing the product of the alternatively spliced ACTN4 transcript (namely, variant actinin-4), and used it to examine the expression of variant actinin-4 immunohistochemically in a total of 609 surgical specimens of various histological subtypes of lung cancer.

Results

Variant actinin-4 was expressed in 55% (96/176) of HGNTs, but in only 0.8% (3/378) of non-neuroendocrine lung cancers. Expression of variant actinin-4 was significantly associated with unfavorable overall survival in HGNT patients (P = 0.00021, log-rank test). Multivariate analysis using the Cox proportional hazards model showed that expression of variant actinin-4 was the most significant independent negative predictor of survival in HGNT patients (hazard ratio, 2.18; P = 0.000714) after the presence of lymph node metastasis (hazard ratio, 2.30; P = 0.00012).

Conclusions

Expression of variant actinin-4 is an independent prognostic factor for patients with HGNTs. This protein has high affinity for filamentous actin polymers and likely promotes aggressive behaviour of cancer cells. The present clinical findings clearly support this notion.

Disclosure

All authors have declared no conflicts of interest.