Rmore, determined by our data, we’re not capable to make further conclusions regarding the molecular underpinnings and probable differences in therapy response of synaptophysin-expressing traditional colorectal adenocarcinomas without a morphologically recognizable neuroendocrine component. Additional studies like clinical trials are required to address this situation. 5. Conclusions In conclusion, we demonstrated that synaptophysin expression in traditional colorectal adenocarcinomas, in contrast to colorectal MANECs, will not be linked with a drastically poorer clinical outcome when in comparison to traditional adenocarcinomas without synaptophysin expression. Consequently, our data strongly suggest that synaptophysin testing really should be restricted to carcinomas whose morphology on H E-stained sections indicates a neuroendocrine differentiation. It also means that conventional adenocarcinomas, in which the cells in the neoplastic glands diffusely express synaptophysin and exceed in quantity the 30 threshold level, shouldn’t be classified as MANECs.Supplementary Materials: The following are obtainable on line at https://www.mdpi.com/article/ 10.3390/cancers13205111/s1. Supplementary Table S1: Clinicopathological traits on the general cohort including traditional adenocarcinomas and MANECs with respect to survival MPEG-2000-DSPE Epigenetic Reader Domain parameters (all round, disease-specific, disease-free survival). Supplementary Table S2: Effect of synaptophysin expression groups on survival parameters in conventional adenocarcinomas using a non-neuroendocrine morphology (log-rank test). Supplementary Table S3: Effect of synaptophysin expression groups on survival parameters in adenocarcinomas using a non-neuroendocrine morphology in comparison to MANECs (log-rank test). Supplementary Table S4: Multivariate evaluation for disease-specific survival like synaptophysin expression groups in conventional adenocarcinomas using a non-neuroendocrine morphology when compared with MANECs like UICC stage, WHO grade, age and sex. Supplementary Figure S1: Overview of synaptophysin staining patterns. Author Contributions: M.J. developed the study; M.J. and B.K. wrote the manuscript with help from G.K., A.K., S.F., S.L., A.v.W., C.D. (Carsten Denkert), W.W., M.J., B.K., A.K., F.S. and M.S. performed histopathological analyses. M.J., C.D. (Carsten Denkert), S.F., W.W. and P.J. performed statistical analyses. M.J., D.W., S.L., G.K., T.G., L.M.S., K.S. (Kristina Schwamborn), C.L., C.D. (Claire Delbridge), A.K., F.S. and K.S. (Katja Steiger). collected clinicopathological data. All authors have read and agreed to the published version of your manuscript.Cancers 2021, 13,13 ofFunding: This research was funded by grants of the Deutsche Forschungsgemeinschaft (DFG, German Investigation Foundation) (project ID 360372040–SFB 1335 to W.W. and project ID 39535707– SFB 1371 to K.S.). The authors have disclosed that they have no substantial relationships with, or financial interest in, any commercial corporations pertaining to this short article. Institutional Evaluation Board Statement: The study was performed in line with the guidelines on the Declaration of Helsinki. The local ethics committee with the Technical University of Munich approved this study (2016-12-14; reference number: 252/16 s). Informed Consent Statement: Patients signed a basic informed consent protocol through admission to the hospital. Data Availability Statement: All information relevant for this study are given using the major paper which includes figures, tables along with the su.
