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.

Citation Format: Akihiko Miyanaga, Kazufumi Honda, Koji Tsuta, Mari Masuda, Akitomo Miyamoto, Shingo Shinagawa, Hitoshi Tsuda, Hisao Asamura, Akihiko Gemma, Tesshi Yamada. Prognostic significance of the alternatively spliced ACTN4 variant in high-grade neuroendocrine pulmonary tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2375. doi:10.1158/1538-7445.AM2013-2375

Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.