Pancreatic undifferentiated carcinoma with osteoclast-like giant cells is genetically similar to, but clinically distinct from, conventional ductal adenocarcinoma.

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGCs, including the whole exome sequencing of eight UCOGCs. We observed that 60% of the UCOGCs contained a well-defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm. The genetic alterations in UCOGC are strikingly similar to those known to drive conventional PDAC, including activating mutations in the oncogene KRAS and inactivating mutations in the tumor suppressor genes CDKN2A, TP53, and SMAD4. These results further support the classification of UCOGC as a PDAC variant and suggest that somatic mutations are not the determinants of the unique phenotype of UCOGC. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Luchini C ，Pea A ，Lionheart G ，Mafficini A ，Nottegar A ，Veronese N ，Chianchiano P ，Brosens LA ，Noë M ，Offerhaus GJA ，Yonescu R ，Ning Y ，Malleo G ，Riva G ，Piccoli P ，Cataldo I ，Capelli P ，Zamboni G ，Scarpa A ，Wood LD ... -  《-》

PD-1, PD-L1, and CD163 in pancreatic undifferentiated carcinoma with osteoclast-like giant cells: expression patterns and clinical implications.

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.

Luchini C ，Cros J ，Pea A ，Pilati C ，Veronese N ，Rusev B ，Capelli P ，Mafficini A ，Nottegar A ，Brosens LAA ，Noë M ，Offerhaus GJA ，Chianchiano P ，Riva G ，Piccoli P ，Parolini C ，Malleo G ，Lawlor RT ，Corbo V ，Sperandio N ，Barbareschi M ，Fassan M ，Cheng L ，Wood LD ，Scarpa A ... -  《-》

Negative prognostic impact of PD-L1 expression in tumor cells of undifferentiated (anaplastic) carcinoma with osteoclast-like giant cells of the pancreas: study of 13 cases comparing ductal pancreatic carcinoma and review of the literature.

Hrudka J ，Lawrie K ，Waldauf P ，Ciprová V ，Moravcová J ，Matěj R ... -  《-》

Undifferentiated Carcinoma with Osteoclast-like Giant Cells of the Pancreas: Molecular Genetic Analysis of 13 Cases.

Hrudka J ，Kalinová M ，Ciprová V ，Moravcová J ，Dvořák R ，Matěj R ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Epithelial-mesenchymal transition in undifferentiated carcinoma of the pancreas with and without osteoclast-like giant cells.

Mattiolo P ，Fiadone G ，Paolino G ，Chatterjee D ，Bernasconi R ，Piccoli P ，Parolini C ，El Aidi M ，Sperandio N ，Malleo G ，Salvia R ，Brosens LA ，Wood LD ，Scarpa A ，Lawlor RT ，Luchini C ... -  《-》