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. 2018 Dec 13;8:17812. doi: 10.1038/s41598-018-36129-1

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© The Author(s) 2018

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Expression of PD-1 is associated to increased malignancy in patients with GEP-NETs. (a,e) CD3, (b,f) FOXP3, (c,g) PD-1 and (d,h) PD-L1 were measured by IHC in a set of TMAs (n = 164) of GEP-NETs. Values represent boxplot of CD3 IHC score and bar graphs of the percentage of samples with positivity for PD-1, FOXP3 and PD-L1 expression. (a–d) Samples were classified based on metastases status at diagnosis: patients with metastasis (MET) or without metastasis (No MET). (e–h) Samples were classified based on the disease status at follow-up evaluation: (1) non-residual disease, if a complete resection after surgery had been achieved and no tumor relapse/recurrence was evidenced; (2) stable disease, in cases of residual but non-progressive tumor burden; and (3) progressive disease, if tumor growth or new lesions were detected. The median of follow-up was 4.9 years (p25: 2.6–p75: 8.6 years). Asterisks indicate significant differences (p-value for Fisher’s Exact Test: *p < 0.05).