000K  utf8
1100  $c2021
1500  eng
2050  urn:nbn:de:gbv:8:3-2021-00814-4
2051  10.3390/cancers13205111
3000  Konukiewitz, Björn
3010  Delbridge, Claire
3010  Denkert, Carsten
3010  Foersch, Sebastian
3010  Groll, Tanja
3010  Jank, Paul
3010  Jesinghaus, Moritz
3010  Kasajima, Atsuko
3010  Klöppel, Günter
3010  Lang, Corinna
3010  Lange, Peter-Sebastian
3010  Schicktanz, Felix
3010  Schmitt, Maxime
3010  Schütze, Lisa Marie
3010  Schwamborn, Kristina
3010  Steiger, Katja
3010  von Werder, Alexander
3010  Weichert, Wilko
3010  Werder, Alexander von
3010  Wilhelm, Dirk
4000  Neuroendocrine Differentiation in Conventional Colorectal Adenocarcinomas$dIncidental Finding or Prognostic Biomarker?  [Konukiewitz, Björn]
4209  Background Colorectal mixed adenoneuroendocrine carcinomas (MANECs) are clinically highly aggressive neoplasms. MANECs are composed of variable adenocarcinoma components combined with morphologically distinct neuroendocrine carcinoma components, which are confirmed by synaptophysin immunohistochemistry, the gold standard marker of a neuroendocrine differentiation. However, the biological behavior of adenocarcinomas that express synaptophysin but do not show a typical neuroendocrine morphology remains unclear. Methods We investigated synaptophysin expression in 1002 conventional colorectal adenocarcinomas and correlated the results with clinicopathological characteristics and patient survival and compared the survival characteristics of synaptophysin expression groups to MANECs. Results Synaptophysin expression in conventional colorectal adenocarcinomas was associated with a shortened disease-free survival (p = 0.037), but not with overall survival or disease-specific survival (DSS) in univariate analyses and without any survival impact in multivariate analyses. Patients with "true" MANECs, on the other hand, showed a significantly shorter survival than all conventional adenocarcinomas with or without synaptophysin expression in uni- and multivariate analyses (e.g., multivariate DSS: p < 0.001, HR: 5.20). Conclusions Our study demonstrates that synaptophysin expression in conventional colorectal adenocarcinomas, in contrast to MANECs, is not associated with a significantly poorer clinical outcome when compared to adenocarcinomas without synaptophysin expression. Furthermore, our data suggest that conventional adenocarcinomas with a diffuse synaptophysin expression should not be classified as MANECs, also strongly arguing that synaptophysin testing should be reserved for carcinomas with an H&E morphology suggestive of a neuroendocrine differentiation.
4209  Simple Summary Colorectal MANECs are highly aggressive carcinomas defined by a distinct neuroendocrine morphology and positivity for synaptophysin in the neuroendocrine component. It is unclear whether a neuroendocrine differentiation in conventional adenocarcinomas without a suggestive morphology is of clinical relevance. We tested 1002 conventional colorectal carcinomas with a non-neuroendocrine morphology for synaptophysin expression and correlated the results with clinicopathological characteristics as well as patient survival and compared the survival characteristics of synaptophysin expression groups to those of true MANECs. We found no survival differences between synaptophysin expression groups within conventional colorectal adenocarcinomas. MANECs, on the other hand, showed significantly worse survival characteristics. Our data suggest that synaptophysin expression in conventional colorectal adenocarcinomas is of minor prognostic relevance and that conventional adenocarcinomas with a diffuse synaptophysin expression should not be classified as MANECs. Abstract Background: Colorectal mixed adenoneuroendocrine carcinomas (MANECs) are clinically highly aggressive neoplasms. MANECs are composed of variable adenocarcinoma components combined with morphologically distinct neuroendocrine carcinoma components, which are confirmed by synaptophysin immunohistochemistry, the gold standard marker of a neuroendocrine differentiation. However, the biological behavior of adenocarcinomas that express synaptophysin but do not show a typical neuroendocrine morphology remains unclear. Methods: We investigated synaptophysin expression in 1002 conventional colorectal adenocarcinomas and correlated the results with clinicopathological characteristics and patient survival and compared the survival characteristics of synaptophysin expression groups to MANECs. Results: Synaptophysin expression in conventional colorectal adenocarcinomas was associated with a shortened disease-free survival (p = 0.037), but not with overall survival or disease-specific survival (DSS) in univariate analyses and without any survival impact in multivariate analyses. Patients with “true” MANECs, on the other hand, showed a significantly shorter survival than all conventional adenocarcinomas with or without synaptophysin expression in uni- and multivariate analyses (e.g., multivariate DSS: p < 0.001, HR: 5.20). Conclusions: Our study demonstrates that synaptophysin expression in conventional colorectal adenocarcinomas, in contrast to MANECs, is not associated with a significantly poorer clinical outcome when compared to adenocarcinomas without synaptophysin expression. Furthermore, our data suggest that conventional adenocarcinomas with a diffuse synaptophysin expression should not be classified as MANECs, also strongly arguing that synaptophysin testing should be reserved for carcinomas with an H&E morphology suggestive of a neuroendocrine differentiation.
4950  https://doi.org/10.3390/cancers13205111$xR$3Volltext$534
4950  https://nbn-resolving.org/urn:nbn:de:gbv:8:3-2021-00814-4$xR$3Volltext$534
4961  https://macau.uni-kiel.de/receive/macau_mods_00002150
5051  610
5550  Colorectal Adenocarcinomas
5550  Manec
5550  Neuroendocrine Differentiation