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Ull block H E slides from 1013 colorectal carcinomas that had been (largely) part of a previously published collective have been rescreened on complete block slides in the beginning of this study [4], where the carcinomas had been re-classified in accordance with the subtypes listed within the 2019 WHO classification of tumors in the digestive method. Tumors that had been not a part of the preceding cohort but added towards the collective had been classified as described previously [4]. The final investigated cohort comprised 1002 colorectal ��-Amanitin Formula adenocarcinomas of a variety of subtypes that showed no morphologic features suggestive of a neuroendocrine carcinoma (Figure 1). Eleven colorectal cancers have been 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 line with existing WHO recommendations (Figure 2). These 11 colorectal MANECs were used as a statistical control group for further analyses.Cancers 2021, 13, xCancers 2021, 13,five of4 ofFigure 1. Synaptophysin-expressing groups in traditional colorectal adenocarcinomas with non-neuroendocrine morphology. (A ) Traditional colorectal adenocarcinoma with Figure 1. Synaptophysin-expressing groups in standard colorectal adenocarcinomas with aanon-neuroendocrine morphology. (A ) Conventional colorectal adenocarcinoma using a a non-neuroendocrine morphology (partial synaptophysin expression group; 109 ) H E (A (2 (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 on the entire tumor. (E ) Conventional colorectal adenocarcinoma with a non-neuroendocrine morphology having a diffuse group of synaptophysin-positive cells accounting for 15 from the whole tumor. (E ) Standard colorectal adenocarcinoma having 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 (two, 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 Scanning magnification (A, HE, two synaptophysin, 2 of a correct colorectal MANEC Figure 2.two. Scanning magnification (A, HE,two B,B, synaptophysin, 2 of a true colorectal MANEC (blue arrow: NEC, black arrow: adenocarcinoma component). Higher magnification in the NEC (blue arrow: NEC, black arrow: adenocarcinoma component). Larger magnification from the NEC element on H E (C, 20 and synaptophysin staining (D, 20 displaying the standard NEC morcomponent on H E (C, 20 and synaptophysin staining (D, 20 displaying the typical NEC morphology. Higher magnification phology. Larger magnification with the poorly differentiated, synaptophysin-negative adenocarcinoma the poorly differentiated, synaptophysin-negative adenocarcinoma componentHE, HE, 20 synaptophysin, 20 ofof this colorectal MANECthat will not show a component (E, (E, 20 F, F, synaptophysin, 20 this colorectal MANEC that does not show a neuroendocrine histomorphology. neuroendocrine histomorphology.two.1.two. Immunohistochemistry 2.1.two. Immunohistochemistry The TMA was stained with synaptophysin (polyclonal, Ventana health-related systems, The TMA was stained with Daunorubicin Cell Cycle/DNA Damage synaptop.

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