Actinin-4 splice variant - A complementary diagnostic and prognostic marker of pancreatic neuroendocrine neoplasms

Xiaojun Xu, Kazufumi Honda, Nami Miura, Shutaro Hori, Solange Le Blanc, Frank Bergmann, Matthias M. Gaida, Michael Volkmar, Simon Schimmack, Thilo Hackert, Oliver Strobel, Klaus Felix

Research output: Contribution to journalArticle

Abstract

Introduction: For pathological diagnosis of pancreatic neuroendocrine neoplasms (pNENs) the routinely used immunohistochemical markers are chromogranin A (CgA) and synaptophysin (Syn). Their ability as prognostic markers is not well established. A splice variant of actinin-4 (Actn-4sv) was recently found to be an excellent biomarker of neuroendocrine neoplasms of the lung. We aimed to investigate the expression of Actn-4sv in pNENs and evaluate its quality as a biomarker of pNENs. Methods: Paraffin-embedded and frozen tissues specimens from 122 pNENs were analyzed. Western blots were performed to prove and compare the relative amount of Actn-4sv expression in pNENs tissue homogenates. For comparison pancreatic ductal adenocarcinoma (PDAC) and normal pancreatic tissues were analyzed in parallel. Immunohistochemistry (IHC) of paraffin sections of pNENs for Actn-4sv were performed and compared to the classic neuroendocrine markers CgA and Syn. Correlations were calculated between the staining intensity and distribution of Actn-4sv and staging, grading and afflicted lymph nodes respectively. Results: Actn-4sv was expressed in 88.5% (108/122) of pNENs, but not in normal pancreatic tissues (0/14) or PDAC (0/14). Compared to CgA and Syn, Actn-4sv was not detectable in islet cells of the normal pancreas. Staining intensity of Actn-4sv on pNENs negatively correlated to the histological grading (Spearman r=-0.4990, p<0.0001) and staging (r = -0.2581, p = 0.0041) but no correlation to afflicted lymph nodes was found. A significantly better overall survival was observed for pNEN patients with higher expression of Actn-4sv (hazard ratio 2.7; log-rank test p= 0.0349). Conclusions: The expression of Actn-4sv may be an important prognostic factor for patients with pNENs. Its expression correlates with the grading and staging of the tumors.

Original languageEnglish
Pages (from-to)2318-2328
Number of pages11
JournalJournal of Cancer
Volume11
Issue number8
DOIs
Publication statusPublished - 2020

Keywords

  • Actinin-4
  • Actinin-4 splice variant
  • PNEN
  • Survival

ASJC Scopus subject areas

  • Oncology

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    Xu, X., Honda, K., Miura, N., Hori, S., Le Blanc, S., Bergmann, F., Gaida, M. M., Volkmar, M., Schimmack, S., Hackert, T., Strobel, O., & Felix, K. (2020). Actinin-4 splice variant - A complementary diagnostic and prognostic marker of pancreatic neuroendocrine neoplasms. Journal of Cancer, 11(8), 2318-2328. https://doi.org/10.7150/jca.37503