Ull block H E slides from 1013 colorectal carcinomas that have been (largely) part of a previously published collective were rescreened on complete block slides in the starting of this study [4], exactly where the carcinomas were re-classified in accordance using the subtypes listed within the 2019 WHO classification of tumors of the digestive method. Tumors that were not a part of the preceding cohort but added to the collective have been classified as described previously [4]. The final investigated cohort comprised 1002 colorectal adenocarcinomas of many subtypes that showed no morphologic capabilities suggestive of a neuroendocrine carcinoma (Figure 1). Eleven colorectal cancers were diagnosed as MANECs on full block slides as they showed adenocarcinomas that had been mixed with a tumor component 30 that was morphologically suggestive of a neuroendocrine carcinoma and that expressed synaptophysin (and Chromogranin A), in accordance with present WHO recommendations (Figure two). These 11 colorectal MANECs have been employed as a statistical manage group for additional analyses.Cancers 2021, 13, xCancers 2021, 13,5 of4 ofFigure 1. Synaptophysin-expressing groups in traditional colorectal adenocarcinomas with non-neuroendocrine morphology. (A ) Conventional colorectal c-di-AMP Metabolic Enzyme/Protease adenocarcinoma with Figure 1. Synaptophysin-expressing groups in standard 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 (two, C (20, (40) and synaptophysin staining (B (two, 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 (2,D (20, F (40) with a group of synaptophysin-positive cells accounting for 15 of the whole tumor. (E ) Traditional colorectal adenocarcinoma using a non-neuroendocrine morphology using a diffuse group of synaptophysin-positive cells accounting for 15 on the whole tumor. (E ) Traditional colorectal adenocarcinoma with a non-neuroendocrine morphology with 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 (two, I (20, K (40) and synaptophysin staining (H (2, J (20, L (40).Cancers 2021, 13, xCancers 2021, 13,six of5 ofFigure Ionomycin Protocol Scanning magnification (A, HE, 2 synaptophysin, 2 of a true colorectal MANEC Figure 2.2. Scanning magnification (A, HE,2 B,B, synaptophysin, 2 of a accurate colorectal MANEC (blue arrow: NEC, black arrow: adenocarcinoma component). Higher magnification of your NEC (blue arrow: NEC, black arrow: adenocarcinoma element). Higher magnification on 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 standard NEC morphology. Larger magnification phology. Greater magnification from the poorly differentiated, synaptophysin-negative adenocarcinoma the poorly differentiated, synaptophysin-negative adenocarcinoma componentHE, HE, 20 synaptophysin, 20 ofof this colorectal MANECthat does not show a component (E, (E, 20 F, F, synaptophysin, 20 this colorectal MANEC that doesn’t show a neuroendocrine histomorphology. neuroendocrine histomorphology.2.1.two. Immunohistochemistry 2.1.two. Immunohistochemistry The TMA was stained with synaptophysin (polyclonal, Ventana health-related systems, The TMA was stained with synaptop.