Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma Journal Article

Authors: Lee, L. H.; Cavalcanti, M. S.; Segal, N. H.; Hechtman, J. F.; Weiser, M. R.; Smith, J. J.; Garcia-Aguilar, J.; Sadot, E.; Ntiamoah, P.; Markowitz, A. J.; Shike, M.; Stadler, Z. K.; Vakiani, E.; Klimstra, D. S.; Shia, J.
Article Title: Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma
Abstract: Immune checkpoint blockade targeting the programmed death-1 (PD-1) pathway has shown efficacy in several types of cancers including mismatch-repair-deficient colorectal carcinoma. In some tumor types, programmed death-ligand 1 (PD-L1) expression detected by immunohistochemistry has shown utility as a predictive marker for response to anti-PD-1 therapies. This utility, however, remains to be determined in colorectal carcinoma. In addition, although tumor-infiltrating lymphocytes have been associated with better prognosis in colorectal carcinoma, the prognostic value of PD-1 expression in these lymphocytes and its interaction with PD-L1 expression still await investigation. To address these questions, we performed a pilot study to evaluate the patterns of PD-L1 and PD-1 immunohistochemical expression on colorectal carcinoma cells and their tumor-infiltrating lymphocytes, respectively. Using tissue microarray, we found that 5% (19/394) of colorectal carcinomas exhibited high tumor PD-L1 expression, and 19% (76/392) had elevated numbers of PD-1-positive tumor-infiltrating lymphocytes. PD-L1 levels correlated with PD-1 levels (P<0.001), and mismatch-repair-deficient tumors had significantly higher rates of high PD-L1 and PD-1 expression when compared with mismatch-repair-proficient tumors (18% vs 2% and 50% vs 13%, respectively; P<0.001 for both). Staining intensity was also stronger for both markers in mismatch-repair-deficient tumors. Furthermore, we observed that among patients with mismatch-repair-deficient colorectal carcinoma, PD-1/PD-L1 expression stratified recurrence-free survival in an inter-dependent manner: an association between high PD-1-positive tumor-infiltrating lymphocytes and improved recurrence-free survival (P=0.041) was maintained only when the tumors had low-level PD-L1 expression (P=0.006); patients whose tumors had both high PD-1-positive tumor-infiltrating lymphocytes and high PD-L1 expression had a significantly worse recurrence-free survival (P<0.001). Thus, our results not only provide a foundation for further assessment of PD-L1 immunohistochemistry as a predictive marker for anti-PD-1 therapy in colorectal carcinoma, they also shed light on the prognostic impact of tumor-infiltrating lymphocytes in different subsets of mismatch-repair-deficient colorectal carcinomas. © 2016 USCAP, Inc All rights reserved.
Journal Title: Modern Pathology
Volume: 29
Issue: 11
ISSN: 0893-3952
Publisher: Nature Publishing Group  
Date Published: 2016-11-01
Start Page: 1433
End Page: 1442
Language: English
DOI: 10.1038/modpathol.2016.139
PROVIDER: scopus
PMCID: PMC5083129
PUBMED: 27443512
Notes: Article -- Export Date: 6 December 2016 -- Source: Scopus
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MSK Authors
  1. Moshe Shike
    105 Shike
  2. Arnold J Markowitz
    109 Markowitz
  3. Neil Howard Segal
    105 Segal
  4. Zsofia Kinga Stadler
    148 Stadler
  5. David S Klimstra
    849 Klimstra
  6. Jinru Shia
    459 Shia
  7. Martin R Weiser
    344 Weiser
  8. Efsevia Vakiani
    163 Vakiani
  9. Jaclyn Frances Hechtman
    104 Hechtman
  10. Jesse Joshua Smith
    48 Smith
  11. Eran Sadot
    36 Sadot
  12. Lik Hang   Lee
    13 Lee