Stains
PDL1 22C3


Topic Completed: 1 February 2016

Minor changes: 2 June 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed Search: PDL1 [title]

Angela M.Y. Chan, M.Sc.
Page views in 2019: 8,021
Page views in 2020 to date: 3,478
Cite this page: Chan A, Enwere E. PDL1 22C3. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsPDL1.html. Accessed June 7th, 2020.
Definition / general
  • Gene symbol PDCD1LG1 stands for Programmed Cell Death Protein 1 (PDCD1, or PD1) Ligand 1
    • The common term PDL1 stands for Programmed Death Ligand 1
  • It is a member of the B7 family of membrane bound, cell surface ligands
  • Mouse PDL1 is 70% identical to human PDL1
  • The primary receptor for PDL1 is PD1
    • PDL2, a homolog of PDL1, also binds to PD1
  • PDL1 is upregulated in monocytes and other cell types by treatment with interferon gamma (IFN7γ)
  • PDL1 protein is expressed in most human cancers but not in most normal tissues (Nat Med 2002;8:793)
Terminology
  • Alternative names are PDCD1 Ligand 1, PDCD1L1, CD274 or B7H1 (OMIM - PCD1)
Pathophysiology
  • The normal function of the PDL1-PD1 interaction is to protect the host from autoreactive T cells
  • The interaction between PDL1 on presenting cells and PD1 on T cells inhibits T cell activation and cytotoxic T lymphocyte mediated lysis (Nat Med 2002;8:793, Nat Med 1999;5:1365)
  • Binding of PDL1 to PD1 also suppresses T cell migration, suppresses proliferation and secretion of cytotoxic mediators, and restricts tumor cell killing
Clinical features
  • PDL1 expression is detected in most human cancers, including bladder, breast, cervical, esophageal, gastric, kidney, lung, ovary and pancreatic cancers
  • High expression of PDL1 is associated with reduced numbers of tumor infiltrating lymphocytes and poor prognosis (Nat Rev Immunol 2008;8:467), although the reverse has also been noted (Histopathology 2016;69:25)
Uses by pathologists
  • Pembrolizumab and nivolumab are monoclonal antibodies which block the interaction between PDL1 and PD1, and have received FDA approval for specific indications (see below)
  • Pembrolizumab is approved for first line treatment of advanced melanoma
    • Also for second or third line treatment of non small cell lung cancer, but specimens must test positive for PDL1 using a companion FDA approved diagnostic IHC test (DAKO PDL1 IHC 22C3 pharmDx)
    • The recommended cutoff for positive staining using the 22C3 antibody is >50% at any intensity
  • Nivolumab is approved for first line treatment of melanoma, second or third line treatment of non small cell lung cancer, and second or third line treatment of advanced renal cell carcinoma without the requirement for a PDL1 diagnostic test (DAKO PDL1 IHC 28-8 pharmDx), although testing is highly recommended
    • The suggested cutoff for positive staining using the 28-8 antibody is > 1% at any intensity
  • The one assay-one drug approach is not sustainable, because there are multiple IHC antibodies performed on multiple platforms, each with its own scoring criteria
  • Even with the recommendations provided with the IHC assay kits, there is still NO consensus on which antibodies, staining platforms and cut points are suitable across the board (Arch Pathol Lab Med 2016;140:326)
Microscopic (histologic) images

Contributed by
GenomeMe

Lung (normal), clone IHC411


Contributed by
Andrey Bychkov, M.D., Ph.D.

Lung adenocarcinoma


 Contributed by
 Emeka Enwere, Ph.D.

Missing Image

Placenta



Images hosted on other servers:
Missing Image

Non small cell lung cancer

Positive staining - normal
  • Lung macrophages, salivary gland ducts (subsets of cells)
  • Placenta, spleen (diffuse), tonsil (diffuse)
Positive staining - disease
  • Carcinomas of colorectum, endometrium, liver, lung, ovary, stomach, thyroid
  • Melanoma
Negative staining
  • Bile duct cells and alveolar cells, hepatocytes, squamous epithelium
Sample pathology report
  • Left lung, mass, biopsy:
    • PDL1 IHC: positive (tumor proportion score 15%)
    • PDL1 IHC (clone 22C3, pharmDx) is an FDA approved companion diagnostic for pembrolizumab performed on a Dako Autostainer Link 48. Tumor cells with partial or complete membrane staining of at least 1+ intensity are scored as positive. Scoring is as follows: < 1% negative, 1 - 49% positive, ≥ 50% positive for high expression. The tumor proportion score is estimated by manual quantification. The sample is adequate if ≥ 100 tumor cells are present. Certain tissue processing factors such as decalcification, formalin fixation time outside an acceptable range (4 to 168 hrs), prolonged time to fixation and use of tissue from blocks that are 5 years or older can affect PDL1 staining and results should be interpreted with caution in such instances. This assay is not validated for decalcified specimens. Pembrolizumab (KEYTRUDA®) is indicated for the treatment of patients with metastatic non small cell lung carcinoma that is positive for high expression of PDL1 (tumor proportion score ≥ 50%), no EGFR or ALK mutation / rearrangement and no prior systemic chemotherapy for metastatic non small cell lung carcinoma. Pembrolizumab is indicated for the treatment of patients with metastatic non small cell lung carcinoma that is positive for PDL1 (tumor proportion score ≥ 1%) and had disease progression on or after platinum containing chemotherapy. Patients with EGFR or ALK mutation / rearrangement should have disease progression on an FDA approved targeted therapy prior to receiving pembrolizumab. PDL1 IHC serves as a complementary diagnostic test for other PDL1 / PD1 targeted therapies.
Back to top