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

• Verfasst von: Xu, Xiaojun [VerfasserIn]
• Verfasst von: Honda, Kazufumi [VerfasserIn]
• Verfasst von: Miura, Nami [VerfasserIn]
• Verfasst von: Le Blanc, Solange [VerfasserIn]
• Verfasst von: Bergmann, Frank [VerfasserIn]
• Verfasst von: Gaida, Matthias [VerfasserIn]
• Verfasst von: Volkmar, Michael [VerfasserIn]
• Verfasst von: Schimmack, Simon [VerfasserIn]
• Verfasst von: Hackert, Thilo [VerfasserIn]
• Verfasst von: Strobel, Oliver [VerfasserIn]
• Verfasst von: Felix, Klaus M. [VerfasserIn]
• Titel: Actinin-4 splice variant - a complementary diagnostic and prognostic marker of pancreatic neuroendocrine neoplasms
• Verf.angabe: 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
• E-Jahr: 2020
• Jahr: 2020-2-10
• Umfang: 11 S.
• Teil: volume:11
• Teil: year:2020
• Teil: number:8
• Teil: pages:2318-2328
• Teil: extent:11
• Fussnoten: Gesehen am 14.04.2020
• Titel Quelle: Enthalten in: Journal of cancer
• Ort Quelle: Wyoming, NSW : Ivyspring Internat. Publ., 2010
• Jahr Quelle: 2020
• Band/Heft Quelle: 11(2020), 8, Seite 2318-2328
• ISSN Quelle: 1837-9664
• DOI: doi:10.7150/jca.37503
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: actinin-4
• Sach-SW: actinin-4 splice variant
• Sach-SW: chromogranin-a
• Sach-SW: clinical utility
• Sach-SW: expression
• Sach-SW: pNEN
• Sach-SW: protein
• Sach-SW: survival
• Sach-SW: tumors
• K10plus-PPN: 1694490475

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.