Cellular localization of PD-L1 expression in mismatch-repair-deficient and proficient colorectal carcinomas.

Autor: Liu S; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Gӧnen M; Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Stadler ZK; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Weiser MR; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Hechtman JF; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Vakiani E; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Wang T; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Vyas M; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Joneja U; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Al-Bayati M; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Segal NH; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Smith JJ; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., King S; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Guercio S; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Ntiamoah P; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Markowitz AJ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Zhang L; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Cercek A; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Garcia-Aguilar J; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Saltz LB; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Diaz LA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Klimstra DS; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Shia J; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. shiaj@mskcc.org.
Jazyk: angličtina
Zdroj: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2019 Jan; Vol. 32 (1), pp. 110-121. Date of Electronic Publication: 2018 Aug 30.
DOI: 10.1038/s41379-018-0114-7
Abstrakt: Blockade of the interaction between PD-1 and its ligands PD-L1 has shown clinical efficacy across several tumor types, especially in mismatch-repair-deficient colorectal carcinoma. The aim of this study was to examine the pattern and cellular localization of PD-L1 expression in the different molecular subtypes of mismatch-repair-deficient colorectal cancers vs. their mismatch-repair-proficient counterparts. PD-L1/SATB2 double-antibody-immunohistochemistry was utilized to distinguish tumor cell from immune cell staining. We observed in our series of 129 colorectal adenocarcinomas that PD-L1 expression occurred primarily in tumor-associated-immune cells and most prominently at the tumor-stroma-interface of the invasive front. The level of invasive front immune cell staining was significantly higher in mismatch-repair-deficient tumors compared to mismatch-repair-proficient tumors (p < 0.001), but no difference was observed among the different subtypes of mismatch-repair-deficient tumors: Lynch syndrome-associated vs. MLH1-methylated vs. unexplained. While selected mismatch-repair-proficient tumors exhibited unusually high tumor-infiltrating-lymphocytes and had high level immune cell PD-L1 expression, a positive correlation between PD-L1 expression and high lymphocyte count was detected only in mismatch-repair-deficient tumors (r = 0.39, p < 0.001) and not in mismatch-repair-proficient tumors. Notably, true tumor cell PD-L1 expression in colorectal carcinoma was rare, present in only 3 of 129 tumors (2.3%): 2 MLH1-methylated and 1 mismatch-repair-proficient with high tumor-infiltrating-lymphocytes; and the staining in the tumor cells in all 3 was diffuse (>=50% of the tumor). These findings may serve to inform further efforts aiming to evaluate PD-L1 immunohistochemistry vis-à-vis molecular sub-classification as predictive biomarkers in the treatment of colorectal carcinoma.
Databáze: MEDLINE
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