Dirk Walter1,2, Eva Herrmann3, Andreas A Schnitzbauer4, Stefan Zeuzem1, Martin Leo Hansmann2, Jan Peveling-Oberhag1,2,5, Sylvia Hartmann2. 1. Department of Internal Medicine I, Frankfurt, Germany. 2. Dr Senckenberg Institute of Pathology, Frankfurt, Germany. 3. Institute of Biostatistics and Mathematical Modelling, Frankfurt, Germany. 4. Department of General and Visceral Surgery, Johann Wolfgang Goethe University Hospital, Frankfurt, Germany. 5. Department for Gastroenterology, Hepatology and Endocrinology, Robert Bosch Hospital, Stuttgart, Germany.
Abstract
AIMS: To investigate the expression of the programmed cell death 1 (PD-1) receptor-programmed cell death ligand 1 (PD-L1) pathway and the clinicopathological characteristics in extrahepatic cholangiocarcinoma (eCCA). METHODS AND RESULTS: Tissue samples from patients with eCCA [n = 69; perihilar cholangiocarcinoma (CCA), 40; and distal CCA, 29] who underwent surgical resection in the period from 2007 to 2015 were evaluated for PD-1, PD-L1, CD3 and CD163 expression, and correlations with clinicopathological characteristics, including survival data, were determined. PD-L1 was found on both tumour cells of eCCA (8/69, 11.6%) and tumour-associated macrophages (21/69, 30.4%). Significant correlations of PD-L1 expression on cancer cells with venous invasion (P = 0.031) and poor differentiation of the tumour (P = 0.048) were observed. In 19 of 69 (27.5%) samples, tumour-infiltrating lymphocytes (TILs) expressed PD-1, whereas infiltration with CD3-positive and CD163-positive cells was found in 63 of 69 (91.3%) and 68 of 69 (98.6%) cases, respectively. The presence of fewer than five CD3-positive cells per high-power field was significantly correlated with poorer differentiation (P = 0.015) and venous invasion (P < 0.001) of CCA. PD-L1 expression was not correlated with patient survival, but PD-L1 expression on tumour cells combined with low infiltration of CD3-positive TILs was associated with an unfavourable outcome (P = 0.027). CONCLUSION: Only a small number of eCCA patients are PD-L1-positive, which might be important for future application of PD-1/PD-L1-targeted immune-modulating therapy in these patients. A small subgroup of eCCAs with PD-L1 expression and low lymphocytic infiltration showed more invasive growth and worse overall survival.
AIMS: To investigate the expression of the programmed cell death 1 (PD-1) receptor-programmed cell death ligand 1 (PD-L1) pathway and the clinicopathological characteristics in extrahepatic cholangiocarcinoma (eCCA). METHODS AND RESULTS: Tissue samples from patients with eCCA [n = 69; perihilar cholangiocarcinoma (CCA), 40; and distal CCA, 29] who underwent surgical resection in the period from 2007 to 2015 were evaluated for PD-1, PD-L1, CD3 and CD163 expression, and correlations with clinicopathological characteristics, including survival data, were determined. PD-L1 was found on both tumour cells of eCCA (8/69, 11.6%) and tumour-associated macrophages (21/69, 30.4%). Significant correlations of PD-L1 expression on cancer cells with venous invasion (P = 0.031) and poor differentiation of the tumour (P = 0.048) were observed. In 19 of 69 (27.5%) samples, tumour-infiltrating lymphocytes (TILs) expressed PD-1, whereas infiltration with CD3-positive and CD163-positive cells was found in 63 of 69 (91.3%) and 68 of 69 (98.6%) cases, respectively. The presence of fewer than five CD3-positive cells per high-power field was significantly correlated with poorer differentiation (P = 0.015) and venous invasion (P < 0.001) of CCA. PD-L1 expression was not correlated with patient survival, but PD-L1 expression on tumour cells combined with low infiltration of CD3-positive TILs was associated with an unfavourable outcome (P = 0.027). CONCLUSION: Only a small number of eCCA patients are PD-L1-positive, which might be important for future application of PD-1/PD-L1-targeted immune-modulating therapy in these patients. A small subgroup of eCCAs with PD-L1 expression and low lymphocytic infiltration showed more invasive growth and worse overall survival.
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