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


Authors: 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.; Diaz, L. A.; Klimstra, D. S.; Shia, J.
Article Title: Cellular localization of PD-L1 expression in mismatch-repair-deficient and proficient colorectal carcinomas
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. © 2018, United States & Canadian Academy of Pathology.
Journal Title: Modern Pathology
Volume: 32
Issue: 1
ISSN: 0893-3952
Publisher: Nature Publishing Group  
Date Published: 2019-01-01
Start Page: 110
End Page: 121
Language: English
DOI: 10.1038/s41379-018-0114-7
PROVIDER: scopus
PMCID: PMC6309293
PUBMED: 30166615
DOI/URL:
Notes: Mod. Pathol. -- Export Date: 2 January 2019 -- Article -- CODEN: MODPE C2 - 30166615 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Leonard B Saltz
    580 Saltz
  2. Arnold J Markowitz
    109 Markowitz
  3. Neil Howard Segal
    101 Segal
  4. Mithat Gonen
    701 Gonen
  5. Liying Zhang
    88 Zhang
  6. Zsofia Kinga Stadler
    144 Stadler
  7. David S Klimstra
    843 Klimstra
  8. Jinru Shia
    450 Shia
  9. Martin R Weiser
    338 Weiser
  10. Efsevia Vakiani
    162 Vakiani
  11. Jesse Joshua Smith
    40 Smith
  12. Sandy Zhuo Liu
    9 Liu
  13. Luis Alberto Diaz
    15 Diaz
  14. Tao Wang
    5 Wang
  15. Sarah A King
    2 King
  16. Monika Vyas
    2 Vyas
  17. Upasana Joneja
    1 Joneja