Cellular localization of PD-L1 expression in mismatch-repair-deficient and proficient colorectal carcinomas.
Publication/Presentation Date
1-1-2019
Abstract
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.
Volume
32
Issue
1
First Page
110
Last Page
121
ISSN
1530-0285
Published In/Presented At
Liu, S., Gӧnen, M., Stadler, Z. K., Weiser, M. R., Hechtman, J. F., Vakiani, E., Wang, T., Vyas, M., Joneja, U., Al-Bayati, M., Segal, N. H., Smith, J. J., King, S., Guercio, S., Ntiamoah, P., Markowitz, A. J., Zhang, L., Cercek, A., Garcia-Aguilar, J., Saltz, L. B., … Shia, J. (2019). Cellular localization of PD-L1 expression in mismatch-repair-deficient and proficient colorectal carcinomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 32(1), 110–121. https://doi.org/10.1038/s41379-018-0114-7
Disciplines
Medicine and Health Sciences
PubMedID
30166615
Department(s)
Department of Pathology and Laboratory Medicine
Document Type
Article