Ull block H E slides from 1013 colorectal carcinomas that have been (mostly) a part of a previously published collective were rescreened on full block slides at the starting of this study [4], where the carcinomas have been re-classified in accordance using the subtypes listed within the 2019 WHO classification of tumors with the digestive program. Tumors that have been not part of the prior cohort but added towards the collective had been classified as described previously [4]. The final investigated cohort comprised 1002 colorectal adenocarcinomas of several subtypes that showed no morphologic attributes suggestive of a neuroendocrine carcinoma (Figure 1). Eleven colorectal cancers were diagnosed as MANECs on complete block slides as they showed adenocarcinomas that have been mixed having a tumor element 30 that was morphologically suggestive of a neuroendocrine carcinoma and that expressed synaptophysin (and Chromogranin A), as outlined by current WHO suggestions (Figure 2). These 11 colorectal MANECs had been employed as a statistical manage group for further analyses.Cancers 2021, 13, xCancers 2021, 13,5 of4 ofFigure 1. Synaptophysin-expressing groups in conventional colorectal adenocarcinomas with non-neuroendocrine morphology. (A ) Standard colorectal adenocarcinoma with Figure 1. Synaptophysin-expressing groups in traditional colorectal adenocarcinomas with aanon-neuroendocrine morphology. (A ) Conventional colorectal adenocarcinoma with a a non-neuroendocrine morphology (partial synaptophysin expression group; 109 ) H E (A (two (2, C (20, (40) and synaptophysin staining (B (2, D (20, F (40) with a non-neuroendocrine morphology (partial synaptophysin expression group; 109 ) onon H E (A, C (20, E E (40) and synaptophysin staining (B (two,D (20, F (40) with a group of synaptophysin-positive cells accounting for 15 of your complete tumor. (E ) Standard colorectal adenocarcinoma with a non-neuroendocrine morphology having a diffuse group of synaptophysin-positive cells accounting for 15 in the whole tumor. (E ) Standard colorectal adenocarcinoma using a non-neuroendocrine morphology having a diffuse synaptophysin expression in all tumor cells on H E (G (2, I (20, K (40) and synaptophysin staining (H (2, J (20, L (40). synaptophysin expression in all tumor cells on H E (G (2, I (20, K (40) and synaptophysin staining (H (two, J (20, L (40).Cancers 2021, 13, xCancers 2021, 13,six of5 ofFigure Scanning magnification (A, HE, 2 synaptophysin, two of a true colorectal MANEC Figure two.2. Scanning magnification (A, HE,2 B,B, synaptophysin, two of a accurate colorectal MANEC (blue arrow: NEC, black arrow: adenocarcinoma component). Higher magnification on the NEC (blue arrow: NEC, black arrow: adenocarcinoma element). Higher magnification with the NEC element on H E (C, 20 and synaptophysin staining (D, 20 showing the standard NEC morcomponent on H E (C, 20 and synaptophysin staining (D, 20 showing the common NEC morphology. Greater magnification phology. Larger magnification of your poorly m-3M3FBS Technical Information differentiated, synaptophysin-negative adenocarcinoma the poorly differentiated, synaptophysin-negative adenocarcinoma componentHE, HE, 20 synaptophysin, 20 ofof this colorectal MANECthat does not show a element (E, (E, 20 F, F, synaptophysin, 20 this colorectal MANEC that does not show a neuroendocrine histomorphology. neuroendocrine histomorphology.two.1.2. Immunohistochemistry two.1.two. Immunohistochemistry The TMA was stained with synaptophysin (polyclonal, Ventana medical systems, The TMA was stained with synaptop.