Stains & molecular markers
PDL1 SP142

Editorial Board Member: Maria Tretiakova, M.D., Ph.D.
Editor-in-Chief: Debra Zynger, M.D.
Gary Tozbikian, M.D.

Topic Completed: 16 June 2020

Minor changes: 16 June 2020

Copyright: 2019-2020, PathologyOutlines.com, Inc.

PubMed Search: PDL1[TI] SP142

Gary Tozbikian, M.D.
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Cite this page: Tozbikian G. PDL1 SP142. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsPDL1SP142.html. Accessed August 11th, 2020.
Definition / general
  • Programmed death ligand 1 (PDL1) is an immune checkpoint protein expressed on activated immune cells and tumor cells (Cancer Epidemiol Biomarkers Prev 2014;23:2965, Cancer Immunol Res 2014;2:361)
  • Coinhibitory factor that binds receptors programmed cell death 1 (PD1) and B7-1 on the surface of activated T cells to regulate the immune response and limit autoimmunity
  • Expression of PDL1 in cancer is an adaptive immune resistance mechanism to avoid T cell mediated anticancer immune response
Essential features
  • PDL1 SP142 is an FDA approved companion diagnostic to atezolizumab for advanced / metastatic triple negative breast cancer (TNBC) and urothelial carcinoma
  • Scoring of PDL1 SP142 expression in triple negative breast cancer and urothelial carcinoma is evaluated in immune cell component using a proportion of tumor area scoring system; cutoffs are tumor site specific
  • SP142 not interchangeable with other PDL1 assays (e.g. 22C3, SP263)
Terminology
  • Alternative names: PDCD1 ligand 1, PDCD1L1, cluster of differentiation 274 (CD274), B7 homolog 1 (B7-H1)
Pathophysiology
  • PDL1 is an immune checkpoint protein that regulates the immune response to prevent excessive / chronic autoimmune inflammation
  • Normally expressed on activated immune cells (e.g. antigen presenting cells and B cells)
  • Expression induced in response to inflammation and high level cytokine expression (IFNγ)
  • Binds regulatory surface receptors PD1 and B7 on CD8+ T cells
  • Inhibits T cell activation and induces T cell exhaustion (Nat Rev Cancer 2012;12:252, Nat Med 2002;8:793)
  • Cancers can express PDL1 as an adaptive immune resistance mechanism to attenuate the host antitumor immune response
  • Selective blockade of the PD1 / PDL1 axis is used as a therapeutic strategy in the treatment of multiple cancers to prevent T cell inhibition and reactivate T cell mediated tumor cell killing
Clinical features
  • PDL1 SP142 is the FDA approved companion diagnostic to atezolizumab
  • FDA approval for atezolizumab + nab-paclitaxel for advanced / metastatic triple negative breast cancer is based on results of the IMpassion130 clinical trial (N Engl J Med 2018;379:2108, Lancet Oncol 2020;21:44)
  • Other non-SP142 PDL1 assays (22C3 and SP263) had low agreement (Annals of Oncology 2019;30:v851)
  • FDA approval for atezolizumab for advanced or metastatic urothelial carcinoma is based on the IMvigor210 clinical trial (Lancet 2017;389:67)
Uses by pathologists
  • Current companion diagnostic indications for VENTANA PDL1 SP142 include advanced / metastatic triple negative breast cancer (TNBC) and urothelial carcinoma
  • PDL1 SP142 assay has FDA regulatory status as a complementary diagnostic for non small cell lung cancer (NSCLC)
Tissue handling
  • VENTANA PDL1 SP142 assay is a qualitative immunohistochemical assay using rabbit monoclonal anti-PDL1 clone SP142 that targets the intracellular domain of PDL1
  • Intended for use in the assessment of PDL1 protein in tumor infiltrating immune cells and in tumor cells in the formalin fixed, paraffin embedded tissues
  • Assay includes OptiView DAB IHC Detection Kit and OptiView Amplification Kit, performed on a VENTANA BenchMark ULTRA instrument
  • Acceptable triple negative breast cancer specimens include primary or metastatic sites; needle biopsies or resection specimens can be used for testing
  • Not validated for cytology specimens
  • Not validated for decalcified specimens
  • Tissue fixed in 10% neutral buffered formalin between 6 - 72 hours
  • Adequacy requires 50 viable tumor cells with associated tumoral stroma
  • Avoid performing on stored precut unstained slides that are older than 2 months
  • Testing must be performed according to standardized analytically validated protocols
  • Recommended control tissue: benign human tonsil
  • Reference: J Thorac Dis 2019;11:S89, Roche: VENTANA PD-L1 (SP142) Assay for Triple-Negative Breast Carcinoma [Accessed 11 May 2020]
Interpretation
  • PDL1 SP142 staining can be present in both immune cell (IC) and tumor cell (TC) components
  • In triple negative breast cancer and urothelial carcinoma, only immune cell staining is counted towards scoring; tumor cell staining is ignored
  • Immune cell staining characteristics (evaluate): punctate, incomplete, membranous staining pattern
  • Tumor cell staining characteristics (ignore): membranous, linear, partial to complete circumferential staining pattern
  • Any degree of intensity staining in immune cells counts towards scoring
  • Any cell type of immune cell staining (e.g. lymphocyte, neutrophil, macrophage) counts towards scoring
  • Avoid scoring in necrotic areas
  • Avoid scoring immune cells within intravascular spaces
  • Scoring method: proportion of tumor area scoring system
    • Calculate the proportion of PDL1 positive tumor infiltrating immune cells as a percentage of total tumor area
  • Total tumor area: defined as the area occupied by tumor cells as well as their associated intratumoral and contiguous peritumoral stroma
  • Triple negative breast cancer:
    • Negative: absence of any discernible staining or presence of discernible staining of any intensity in tumor infiltrating immune cells covering < 1% of tumor area occupied by tumor cells, associated intratumoral and contiguous peritumoral stroma
    • Positive: presence of discernible staining of any intensity in tumor infiltrating immune cells covering ≥ 1% of tumor area occupied by tumor cells, associated intratumoral and contiguous peritumoral stroma
  • Urothelial carcinoma:
    • Negative: absence of any discernible staining or presence of discernible staining of any intensity in tumor infiltrating immune cells covering < 5% of tumor area occupied by tumor cells, associated intratumoral and contiguous peritumoral stroma
    • Positive: presence of discernible staining of any intensity in tumor infiltrating immune cells covering ≥ 5% of tumor area occupied by tumor cells, associated intratumoral and contiguous peritumoral stroma
  • Non small cell lung carcinoma (NSCLC):
    • Step 1: tumor cell staining assessment
      • Positive: presence of discernible membrane staining of any intensity in ≥ 50% of tumor cells
      • Negative: absence of any discernible staining or presence of discernible membrane staining of any intensity in < 50% of tumor cells (proceed to step 2)
    • Step 2: immune cell staining assessment
      • Positive: presence of discernible staining of any intensity in tumor infiltrating immune cells covering ≥ 10% of tumor area occupied by tumor cells, associated intratumoral and contiguous peritumoral stroma
      • Negative: absence of any discernible staining or presence of discernible staining of any intensity in tumor infiltrating immune cells covering < 10% of tumor area occupied by tumor cells, associated intratumoral and contiguous peritumoral stroma
  • Reference: J Thorac Dis 2019;11:S89, Roche: VENTANA PD-L1 (SP142) Assay for Triple-Negative Breast Carcinoma [Accessed 11 May 2020]
Microscopic (histologic) images

Contributed by Gary Tozbikian, M.D.

Triple negative breast carcinoma with PDL1 SP142



Contributed by Maria Tretiakova, M.D., Ph.D.

SP142 expression in bladder cancer

Positive staining - normal
Positive staining - disease
Negative staining
  • Tonsil superficial squamous epithelium (control tissue)
Sample pathology report
  • Right lung, core needle biopsy:
    • Metastatic mammary carcinoma involving lung
    • PDL1 (VENTANA SP142) staining in tumor infiltrating immune cells:
      • Result: positive
      • Proportion of tumor area occupied by PDL1 expressing tumor infiltrating immune cells (percentage IC): 3%
      • Comment: PD-L1 is evaluated by manual quantitative immunohistochemistry on formalin fixed (for >6 and <72 hours if possible), paraffin embedded tissue using the FDA approved clone SP142 (Ventana Medical Systems), OptiView DAB IHC Detection Kit and OptiView Amplification Kit on a Ventana BenchMark ULTRA instrument. The result is reported as proportion of tumor area occupied by PD-L1 expressing tumor infiltrating immune cells (percentage IC) including lymphocytes, macrophages, dendritic cells and granulocytes. Neutrophils in vessels, serum and necrosis are excluded. Tumor area is defined as the area containing viable tumor cells, the associated intratumoral stroma and contiguous peritumoral stroma. Staining is usually punctate but may be circumferential. Staining of any intensity is included. Proportion of tumor area occupied by tumor infiltrating immune cells with expression (percentage IC) is scored as <1% negative or ≥1% positive. If the specimen has been decalcified, exceeds cold ischemic time or is outside the recommended range for formalin fixation time, the results should be interpreted with caution. This assay has not been validated for decalcified specimens, cytology specimens and specimens in which the cold ischemic/fixation time is unknown. All controls show appropriate reactivity. All immunohistochemistry, in situ hybridization and histochemical tests were developed and are performed at the _____ Laboratory. All tests reported here, except those addressing HER2, ALK and PD-L1 expression as predictive markers, have not been cleared by or approved by the US FDA. The laboratory is regulated under CLIA as qualified to perform high complexity testing. The tests are used for clinical purposes. They should not be regarded as investigational or for research.
Board review style question #1

Which of the following statements regarding PDL1 SP142 is correct?

  1. In advanced / metastatic triple negative breast cancer, scoring is determined by using combined positive score (CPS), with a positive score cutoff of CPS ≥ 1
  2. In triple negative breast cancer, valid clinical specimens include cytology specimens
  3. In triple negative breast cancer, scoring is only evaluated in the immune cell component
  4. It is the FDA approved companion diagnostic assay for pembrolizumab
  5. Results of other PDL1 IHC assays (e.g. 22C3) are highly concordant and interchangeable
Board review answer #1
C. PDL1 SP142 is the FDA approved companion diagnostic assay for atezolizumab. In triple negative breast cancer and urothelial carcinoma, SP142 is scored using a tumor area proportion scoring system. Cutoffs are site specific. Both primary and metastatic specimens are acceptable for evaluation, unless the specimen is decalcified. Cytology specimens are generally not validated for SP142 evaluation, due to the requirement of intact tumoral stroma for scoring. Published studies in triple negative breast cancer and other tumors have shown poor concordance of PDL1 SP142 with other PDL1 assays; the results of other non-SP142 PDL1 assays are not interchangeable or equivalent to SP142. In triple negative breast cancer and urothelial carcinoma, SP142 expression can be observed in both immune cell or tumor cell components, however only immune cell staining is counted towards scoring (Mod Pathol 2018;31:13817, N Engl J Med 2018;379:2108, Lancet Oncol 2020;21:44, Annals of Oncology 2019;30:v851).

Reference: PDL1 SP142

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