PD-1, PD-L1, and CD163 in pancreatic undifferentiated carcinoma with osteoclast-like giant cells: A expression patterns and clinical implications
| Autor: | Claudio Luchini, Alessia Nottegar, Antonio Pea, Jérôme Cros, Claudia Parolini, Lodewijk A.A. Brosens, Mattia Barbareschi, Vincenzo Corbo, Rita T. Lawlor, Camilla Pilati, Paola Piccoli, Laura D. Wood, Matteo Fassan, Paola Capelli, Aldo Scarpa, Peter Chianchiano, Giulio Riva, Nicola Sperandio, G. Johan A. Offerhaus, Giuseppe Malleo, Nicola Veronese, Andrea Mafficini, Michaël Noë, Liang Cheng, Borislav Rusev |
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| Přispěvatelé: | Luchini, C., Cros, J., Pea, A., Pilati, C., Veronese, N., Rusev, B., Capelli, P., Mafficini, A., Nottegar, A., Brosens, L.A.A., Noë, M., Offerhaus, G.J.A., Chianchiano, P., Riva, G., Piccoli, P., Parolini, C., Malleo, G., Lawlor, R.T., Corbo, V., Sperandio, N., Barbareschi, M., Fassan, M., Cheng, L., Wood, L.D., Scarpa, A. |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Indiana Programmed Cell Death 1 Receptor Osteoclast PDAC Pancreatic Cancer Tumor-Associated Macrophages UCOGC Osteoclasts Giant Cells B7-H1 Antigen 0302 clinical medicine Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] Lymphocytes Aged 80 and over biology Tumor-associated macrophages Cell Differentiation Middle Aged Pancreatic cancer 2734 Immunohistochemistry Europe Phenotype medicine.anatomical_structure 030220 oncology & carcinogenesis Female Antibody Carcinoma Pancreatic Ductal Adult Antigens Differentiation Myelomonocytic Receptors Cell Surface Pathology and Forensic Medicine 03 medical and health sciences Immune system All institutes and research themes of the Radboud University Medical Center Antigens CD PD-L1 Biomarkers Tumor medicine Humans Histiocyte Aged Neoplasm Staging Histiocytes medicine.disease Pancreatic Neoplasms 030104 developmental biology Giant cell Cancer research biology.protein CD163 |
| Zdroj: | Human Pathology, 81, pp. 157-165 Human Pathology, 81, 157-165 Human Pathology, 81, 157. W.B. Saunders Ltd |
| ISSN: | 0046-8177 |
| Popis: | Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC), a variant of pancreatic ductal adenocarcinoma (PDAC), has a striking genetic similarity to PDAC but a significantly improved overall survival. We hypothesize that this difference could be due to the immune response to the tumor, and as such, we investigated the expression of PD-1, PD-L1, and CD163 in a series of UCOGC. To this aim, 27 pancreatic UCOGCs (11 pure and 16 PDAC-associated), 5 extrapancreatic tumors with osteoclast-like giant cells and 10 pancreatic anaplastic carcinomas were immunostained using antibodies against PD-1, PD-L1, and CD163. In pancreatic UCOGCs, PD-L1 was expressed in neoplastic cells of 17 (63%) of 27 cases, more often in cases with an associated PDAC (P =.04). Expression of PD-L1 was associated with poor prognosis, confirmed by multivariate analysis: patients with PD-L1–positive UCOGCs had a risk of all-cause mortality that was 3 times higher than did patients with PD-L1–negative UCOGCs (hazard ratio, 3.397; 95% confidence interval, 1.023-18.375; P =.034). PD-L1 expression on tumor cells was also associated with aberrant P53 expression (P =.035). PD-1 was expressed on rare lymphocytes in 12 UCOGCs (44.4%), mainly located at the tumor periphery. CD163 was expressed on histiocytes, with a diffuse and strong staining pattern in all UCOGCs. Extrapancreatic tumors with osteoclast-like giant cells showed very similar staining patterns for the same proteins. Anaplastic carcinomas have some similarities to UCOGCs, but PD-L1 has no prognostic roles. Our results may have important implications for immunotherapeutic strategies in UCOGCs; these tumors may also represent a model for future therapeutic approaches against PDAC. © 2018 Elsevier Inc. |
| Databáze: | OpenAIRE |
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