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PD‐L1 Expression in Non‐Small Cell Lung Cancer Specimens : Association with Clinicopathological Factors and Molecular Alterations

Mansour, Mohammed S.I. LU orcid ; Malmros, Karina LU ; Mager, Ulrich ; Lindquist, Kajsa Ericson LU ; Hejny, Kim ; Holmgren, Benjamin ; Seidal, Tomas ; Dejmek, Annika LU ; Dobra, Katalin and Planck, Maria LU , et al. (2022) In International Journal of Molecular Sciences 23(9).
Abstract

Immune checkpoint inhibitors (ICI) targeting programmed cell death‐1 or its ligand (PD‐ L1) have improved outcomes in non‐small cell lung cancer (NSCLC). High tumor PD‐L1 expression, detected by immunohistochemistry (IHC) typically on formalin‐fixed paraffin‐embedded (FFPE) histological specimens, is linked to better response. Following our previous investigation on PD‐L1 in cytological samples, the aim of this study was to further explore the potential impacts of various clinicopathological and molecular factors on PD‐L1 expression. Two retrospective NSCLC cohorts of 1131 and 651 specimens, respectively, were investigated for PD‐L1 expression (<1%/1– 49%/≥50%), sample type, sample site, histological type, and oncogenic driver... (More)

Immune checkpoint inhibitors (ICI) targeting programmed cell death‐1 or its ligand (PD‐ L1) have improved outcomes in non‐small cell lung cancer (NSCLC). High tumor PD‐L1 expression, detected by immunohistochemistry (IHC) typically on formalin‐fixed paraffin‐embedded (FFPE) histological specimens, is linked to better response. Following our previous investigation on PD‐L1 in cytological samples, the aim of this study was to further explore the potential impacts of various clinicopathological and molecular factors on PD‐L1 expression. Two retrospective NSCLC cohorts of 1131 and 651 specimens, respectively, were investigated for PD‐L1 expression (<1%/1– 49%/≥50%), sample type, sample site, histological type, and oncogenic driver status. In both cohorts, PD‐L1 was positive (≥1%) in 55% of the cases. Adenocarcinomas exhibited lower PD‐L1 expression than squamous cell carcinomas (p < 0.0001), while there was no difference between sample types, tumor locations, or between the two cohorts in multivariate analysis (all p ≥ 0.28). Mutational status correlated significantly with PD‐L1 expression (p < 0.0001), with the highest expression for KRASmutated cases, the lowest for EGFR‐mutated, and the KRAS/EGFR wild‐type cases in between. There was no difference in PD‐L1 levels between different prevalent KRAS mutations (all p ≥ 0.44), while mucinous KRAS‐mutated adenocarcinomas exhibited much lower PD‐L1 expression than non‐mucinous (p < 0.0001). Our data indicate that cytological and histological specimens are comparable for PD‐L1 evaluation. Given the impact of KRAS mutations and the mucinous growth pattern on PD‐L1 expression, these factors should be further investigated in studies on ICI response.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
biopsy, cytology, EGFR, histology, KRAS, mucinous, sample site
in
International Journal of Molecular Sciences
volume
23
issue
9
article number
4517
publisher
MDPI AG
external identifiers
  • scopus:85128396649
  • pmid:35562908
ISSN
1661-6596
DOI
10.3390/ijms23094517
project
Biomarkers in mesothelioma and non-small cell lung cancer: Investigation of cytological specimens with correlation to histology
Improvement of diagnostic and prognostic cytopathology of lung cancer and malignant mesothelioma.
language
English
LU publication?
yes
id
a1d718da-ac1e-4c1e-9fa0-6f275bd88850
date added to LUP
2022-06-20 15:43:10
date last changed
2024-06-26 04:52:46
@article{a1d718da-ac1e-4c1e-9fa0-6f275bd88850,
  abstract     = {{<p>Immune checkpoint inhibitors (ICI) targeting programmed cell death‐1 or its ligand (PD‐ L1) have improved outcomes in non‐small cell lung cancer (NSCLC). High tumor PD‐L1 expression, detected by immunohistochemistry (IHC) typically on formalin‐fixed paraffin‐embedded (FFPE) histological specimens, is linked to better response. Following our previous investigation on PD‐L1 in cytological samples, the aim of this study was to further explore the potential impacts of various clinicopathological and molecular factors on PD‐L1 expression. Two retrospective NSCLC cohorts of 1131 and 651 specimens, respectively, were investigated for PD‐L1 expression (&lt;1%/1– 49%/≥50%), sample type, sample site, histological type, and oncogenic driver status. In both cohorts, PD‐L1 was positive (≥1%) in 55% of the cases. Adenocarcinomas exhibited lower PD‐L1 expression than squamous cell carcinomas (p &lt; 0.0001), while there was no difference between sample types, tumor locations, or between the two cohorts in multivariate analysis (all p ≥ 0.28). Mutational status correlated significantly with PD‐L1 expression (p &lt; 0.0001), with the highest expression for KRASmutated cases, the lowest for EGFR‐mutated, and the KRAS/EGFR wild‐type cases in between. There was no difference in PD‐L1 levels between different prevalent KRAS mutations (all p ≥ 0.44), while mucinous KRAS‐mutated adenocarcinomas exhibited much lower PD‐L1 expression than non‐mucinous (p &lt; 0.0001). Our data indicate that cytological and histological specimens are comparable for PD‐L1 evaluation. Given the impact of KRAS mutations and the mucinous growth pattern on PD‐L1 expression, these factors should be further investigated in studies on ICI response.</p>}},
  author       = {{Mansour, Mohammed S.I. and Malmros, Karina and Mager, Ulrich and Lindquist, Kajsa Ericson and Hejny, Kim and Holmgren, Benjamin and Seidal, Tomas and Dejmek, Annika and Dobra, Katalin and Planck, Maria and Brunnström, Hans}},
  issn         = {{1661-6596}},
  keywords     = {{biopsy; cytology; EGFR; histology; KRAS; mucinous; sample site}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{9}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{PD‐L1 Expression in Non‐Small Cell Lung Cancer Specimens : Association with Clinicopathological Factors and Molecular Alterations}},
  url          = {{http://dx.doi.org/10.3390/ijms23094517}},
  doi          = {{10.3390/ijms23094517}},
  volume       = {{23}},
  year         = {{2022}},
}