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. 2021 Mar 18;11:6203. doi: 10.1038/s41598-021-85593-9

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Rb1/p16 pathway deregulation in colorectal NECs revealed by immunohistochemistry and next-generation sequencing. (A) Representative micrograph of small-cell NEC displaying small to medium sized cells with a high nuclear-cytoplasmic ratio, scant cytoplasm and frequent mitotic figures. (B) Representative micrograph of large-cell NEC showing large polygonal cells with prominent nucleoli and moderate amount of eosinophilic cytoplasm. (C) Intense and diffuse nuclear staining for p53. (D) Intense and diffuse cytoplasmic staining for p16. (E) Complete loss of Rb1 expression. (F) Deep deletion of RB1 on a normalized sequencing depth (red circle).