Keytruda (pembrolizumab), Tumor Proportion Score, TPS, Combined Positive Score, CPS, Specimen Collection Criteria
Specimen Collection Criteria
Collect (preferred specimen): Formalin-fixed, paraffin-embedded (FFPE) block with corresponding H&E slide. Tissue should be well fixed and processed. Tissue should not be decalcified. The specimen should not be a cytology specimen. Please provide a pathology report with each specimen, including type of fixative and hours duration of fixation (if known). Tissue must be fixed for a minimum of 3 hours in 10% neutral buffered formalin. Indicate fixation time on test requisition.
Also acceptable: One H&E slide plus 4 unstained tissue section cut at 4.0 um thick and placed on charge slides. Air dry, do not oven dry. Tissue adherence cannot be guaranteed for sections placed on plain glass slides. Send all slides within 6 weeks of cutting.
Specimen must be accompanied by a completed requisition and must contain the patient name, date of birth, collection date, ordering physician, source of specimen, and fixation time, if known. Please provide a pathology report with each specimen.
Alternative (suboptimal specimen): If non-decalcified FFPE tissue is not available, PD-L1 22C3 testing may be attempted on tissue that has been decalcified or on cytologic cell block sections; however, PD-L1 22C3 testing is not FDA-approved for decalcified tissue or cytology cell blocks. It will be stated in the report that PD-L1 22C3 testing on these alternative specimens is not recommended, not validated, and not FDA-approved.
Physician Office/Draw Specimen Preparation
Maintain paraffin-embedded tissue or slides at room temperature (20-26ºC or 68-78.8ºF) until transport.
Preparation for Courier Transport
Transport: Paraffin-embedded tissue or slides at room temperature (20-26ºC or 68-78.8ºF).
- Tissue in fixatives other than 10% neutral buffered formalin. (See above regarding decalcified FFPE tissue and cytology cell blocks).
- Improper labeling, inadequate information.
- Specimens with less than 100 viable tumor cells.
Inpatient Specimen Preparation
Please refer to Surgical Specimen, Routine in the Beaumont Laboratory Test Directory.
Maintain specimens at room temperature (20-26ºC or 68-78.8ºF) until testing.
Specimen Stability for Testing:
Tissue Room Temperature (20-26ºC or 68-78.8ºF): Indefinitely Refrigerated (2-8ºC or 36-46ºF): Unacceptable Frozen (-20ºC/-4ºF or below): Unacceptable
Tissue Section on Glass Slide Room
Temperature (20-26ºC or 68-78.8ºF): 6 weeks Refrigerated (2-8ºC or 36-46ºF): Unacceptable Frozen (-20ºC/-4ºF or below): Unacceptable
Decalcified FFPE tissue blocks or cytologic cell blocks
Room Temperature (20-26ºC or 68-78.8ºF): Indefinitely Refrigerated (2-8ºC or 36-46ºF): Unacceptable Frozen (-20ºC/-4ºF or below): Unacceptable
Specimen Storage in Department Prior to Disposal
Room Temperature (20-26ºC or 68-78.8ºF): 7 days
Royal Oak Anatomic Pathology – Advanced Diagnostics Laboratory.
Daily. Results available in 7 business days for routine cases.
Cut-off values of the reference range are dependent on clinical parameters such as tumor type, patient history and intended pharmaceutical therapeutic agent.
References ranges may change over time. Refer to the most current Keytruda (pembrolizumab) prescribing information document for cutoff values in specific clinical circumstances.
The Tumor Proportion Score (TPS) represents the percentage of viable tumor cells with partial or complete membrane staining relative to all viable tumor cells.
PD-L1 Tumor Proportion Score (TPS) will be reported as a percentage from <1% to 100%.
The Combined Positive Score (CPS) represents the number of PD-L1 staining cells (tumor cells, tumor-associated lymphocytes, and tumor-associated histiocytes) divided by the number of total viable tumor cells, multiplied by 100.
PD-L1 Combined Positive Score (CPS) will be reported as a number from <1 to 100.
If there are insufficient tumor cells for evaluation, this will be stated, and a TPS or CPS will not be reported.
Immunoperoxidase staining and detection of PD-L1 is performed in formalin-fixed, paraffin embedded tissue sections using a polymer based detection system. Four micron tissue sections are deparaffinized, subjected to heat-induced antigen retrieval and then sequentially incubated with anti-PD-L1 monoclonal antibody and followed by a polymer detection reagent. Sections are subsequently treated with chromogen diaminobenzidine and the substrate hydrogen peroxide to produce a brown membranous staining in cells expressing PD-L1. Sections are lightly counterstained in Hematoxylin.
Stained slides are examined by a pathologist who will provide a Tumor Proportion Score (TPS) or Combined Proportion Score (CPS) in the interpretive report. Results are reported based on the interpretation guidelines in the FDA approved PD-L1 IHC 22C3 pharmDx interpretation manuals1-3.
PD-L1 22C3 pharmDx testing is used as an aid in identifying patients with various types of cancer for treatment with Keytruda (pembrolizumab). A minimum of 100 viable tumor cells is required for examination. The PD-L1 22C3 score can be reported as Tumor Proportion Score (TPS) or Combined Positive Score (CPS). Whether to report a TPS or CPS is dependent on tumor specific information from the most current Keytruda (pembrolizumab) prescribing information document. TPS and CPS cutoff values for PD-L1 expression are dependent on the tumor type, and are subject to change. Though every effort is made to have up-to-date tumor specific cutoff values within the PD-L1 22C3 report, the treating physician is directed to refer to the most current Keytruda (pembrolizumab) prescribing information document for appropriate cutoff values.
Tumor types not listed in the most current Keytruda (pembrolizumab) prescribing information document can be tested for PD-L1 22C3; however, the appropriate score type and cutoffs values are unknown. In this scenario, treating physicians are directed to refer to the product label of the pharmaceutical therapeutic agent of interest for cutoff values to guide therapy in specific clinical circumstances.
- PD-L1 IHC 22C3 pharmDx Interpretation Manual – Non-small Cell Lung Cancer, Dako, Agilent Technologies, 2019
- PD-L1 IHC 22C3 pharmDx Interpretation Manual, Gastric or Gastroesophageal Junction Adenocarcinoma, Dako, Agilent Technologies
- PD-L1 IHC 22C3 pharmDx Interpretation Manual, Urothelial Carcinoma, Dako, Agilent Technologies
Technical and Professional: 88360.
Anatomic Pathology – RO
Advanced Diagnostics Lab – RO
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This directory currently reflects information only for specimens collected and/or processed at the
Farmington Hills, Grosse Pointe, Royal Oak, and Troy campuses.