Why two labs gave you different PD-L1 results
Holding two PD-L1 reports that don't match? It happens more than patients expect — PD-L1 immunohistochemistry uses several different antibody clones (22C3, 28-8, SP263, SP142), each validated for a specific drug, and two accredited labs can report modestly different numbers on the very same tissue without either one being wrong. NCCN and ASCO both acknowledge this as a known limitation of PD-L1 testing, not a lab error. This page explains, calmly, why the numbers can differ and what to check before assuming one lab got it wrong — it explains terminology only; only your oncologist can interpret what your specific reports mean for you.
Medically reviewed by Dr. C. Raghavendra Reddy, Medical Oncologist, MBBS (Gold Medal) · DNB · DM (Medical Oncology, Gold Medal) · Last reviewed August 2026
- Different labs, different clones — 22C3, 28-8, SP263 and SP142 aren't interchangeable, and different clones can score the same sample differently
- Not necessarily an error — modest variation between two accredited labs is a published, recognised limitation of PD-L1 testing
- The assay matters more than the lab — check which antibody clone each report used before deciding one lab is "right"
- One number, not the whole picture — your oncologist weighs PD-L1 alongside MSI, TMB, subtype and stage, not in isolation
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Why do two labs give different PD-L1 results?
PD-L1 immunohistochemistry is not one standardised test — it's a family of related assays, each built around a specific antibody clone (22C3, 28-8, SP263 or SP142) validated as a companion diagnostic for a specific drug in a specific cancer's trial. Two accredited labs testing the very same tissue block with different clones can report a modestly different number, and factors such as sample age, tissue quality, and scoring by different pathologists add a further layer of natural variation.
This is openly discussed in NCCN and ASCO guidance as a recognised limitation of PD-L1 as a biomarker — it is why oncologists read a PD-L1 result alongside the assay it came from, rather than treating any single number as an absolute verdict. A difference between two reports is common enough that it rarely means either lab made a mistake.
PD-L1 testing for CION patients is coordinated through accredited partner pathology laboratories that perform the staining and scoring — this page explains the general terminology behind why numbers can vary; it does not interpret your specific reports.
Did you know?
Because PD-L1 assays differ by clone, a pharma-industry consortium ran the "Blueprint" PD-L1 IHC comparability studies starting in 2017, testing multiple clones side-by-side on the same tumour samples — the findings are part of why pathology labs now report the antibody clone used, not just a bare score.
Common PD-L1 antibody clones — what they're validated for
Check your report's methodology line for one of these clone names. Comparing a result from one clone against another is not a like-for-like comparison.
Clones, scoring methods and example companion drugs shown are the commonly cited associations from regulatory companion-diagnostic labelling and NCCN/ASCO guideline references, indicative as of August 2026. Guidelines are updated periodically — your oncologist confirms which assay applies to your specific treatment plan; this table is general education, not an eligibility statement.
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Don't let conflicting numbers cause panic
Bring both reports to a free, confidential consultation. A CION oncologist will explain the likely reason for the difference and what it means for your options.
How do you work out which result to weigh more?
Rather than picking a "winner" between two reports, work through these checks with your oncology team.
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Check the antibody clone on each report
Find the clone name (22C3, 28-8, SP263, SP142) and scoring method (TPS, CPS, IC) in the methodology line of each report — a TPS number from one clone isn't directly comparable to a CPS number from another.
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Confirm whether the samples are the same
Two reports from the same biopsy block should be more directly comparable than reports from different biopsy sites, or from the primary tumour versus a metastasis.
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Note the time gap between samples
PD-L1 expression can genuinely change over months or after treatment — a difference across two timepoints may reflect real biological change, not disagreement between labs.
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Bring both reports to your oncology team
A tumour board weighs both results together, alongside your cancer subtype and other biomarkers, rather than averaging or discarding either number on its own.
So which result should be trusted?
Neither report is automatically the "correct" one. Your oncology team weighs which assay is validated as the companion diagnostic for the specific drug being considered, how recent and how good the tissue quality of each sample was, and whether the two samples came from the same site and timepoint at all. In most cases both reports are read together rather than one being discarded.
Picking the higher or the lower of two numbers yourself, or shopping for a third lab to "settle" the question, usually adds cost and delay without changing the underlying clinical picture — the more useful step is almost always a conversation with your treating oncologist, with both reports in hand.
What else can cause two different PD-L1 numbers?
The antibody clone is the biggest driver, but it isn't the only reason two PD-L1 results can differ.
- Different antibody clone — 22C3, 28-8, SP263 and SP142 are validated for different drugs and are not interchangeable, even on the same tissue.
- Tumour heterogeneity — PD-L1 expression can genuinely vary between different areas of the same tumour, or between the primary tumour and a metastasis.
- Time between samples — expression can change after chemotherapy or radiation, or simply between diagnosis and a later relapse.
- Sample age and quality — smaller biopsies or tissue fixed and stored for longer can stain less reliably than a fresh, adequate sample.
- Scoring variability — PD-L1 scoring is done by a trained pathologist under a microscope, and some inter-observer variation is expected even with the same clone.
Understanding the wider biomarker picture
- Biomarkers Beyond PD-L1: What Else Predicts Response — why PD-L1 is only one of several tests your oncologist may weigh.
- Tumour-Agnostic Treatment: When the Biomarker Matters More Than the Cancer — biomarkers, like MSI-High, that can matter independently of PD-L1 or cancer type.
- What Is EBV, HPV or Hepatitis Status Got to Do With Immunotherapy? — other lab results your oncology team may check alongside PD-L1.
- Immunotherapy at CION Cancer Clinics — the full picture of how CION supports patients through the immunotherapy decision and journey.
This page explains general reasons PD-L1 results can differ between labs, for education only, and does not interpret any individual patient's report. PD-L1 testing is coordinated at accredited partner pathology laboratories. Bring both reports to a consultation for a doctor's assessment of what they mean for you.
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