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IHC Markers Explained

Why IHC Results — Differ Between Labs

Finding different IHC numbers on two reports from two labs feels like someone has made a mistake. Usually no mistake has been made. Labs use different validated methods, and your oncologist is trained to interpret results knowing which method your lab used.

Medically reviewed by Dr. C. Raghavendra Reddy, Medical Oncologist, MBBS (Gold Medal) · DNB · DM (Medical Oncology, Gold Medal) · Last reviewed September 2026

  • Different clones, same target — Labs use different manufacturers' antibody clones that are each validated but not identical. The same protein can score differently depending on which clone was used.
  • Scoring systems are not interchangeable — An Allred score, an H-score, and a percentage positive all measure the same protein but cannot be directly converted across one another.
  • PD-L1 clones are a special case — PD-L1 testing uses clones validated in different contexts with different scoring methods. The clone your lab used changes how the number should be read.
  • Variation is expected, not an error — Inter-laboratory variation in IHC is documented and expected by professional pathology bodies. Your oncologist interprets results in the context of your lab's specific method.
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IHC results can differ between labs because each lab uses its own antibody clone, staining platform, and scoring method. These are all validated approaches that can produce genuinely different numbers from the same tissue. Your oncologist interprets your result knowing which assay your lab used — not as a standalone number.

What do the terms on your IHC report mean?

IHC (immunohistochemistry)
A laboratory method that uses antibodies to detect specific proteins in a thin slice of your tumour tissue. The result tells your oncologist whether a protein is present, absent, or active in your cancer cells.
Antibody clone
The specific antibody version a lab uses to detect a protein. Different manufacturers produce different clones, each calibrated differently, so the same protein can score differently between labs.
Scoring system
The method used to measure how much of a protein is present. ER can be expressed as an Allred score, an H-score, or a percentage of positive cells. These are not directly convertible from one to another.
NABL accreditation
Independent audit confirming a lab meets national quality standards. It means the lab runs its own validated method consistently — not that all NABL labs use identical reagents or reach identical results.
Companion diagnostic
A test designed and validated specifically alongside a particular treatment in clinical trials. The positivity threshold was set using that assay — substituting a different assay may not produce an equivalent result.

What should I ask about my IHC report?

  • Ask which antibody clone the lab used — the report should name it
  • Check whether the scoring system is documented — Allred score, H-score, or percentage positive
  • Note whether the lab holds NABL accreditation
  • Tell your oncologist if you have results from more than one lab
  • Ask your oncologist which result they are using for treatment decisions

Why do the same cells produce different numbers?

Your tumour tissue does not change between labs — but the reagents, instruments, and reference systems do. Two validated tests of the same protein are like two calibrated thermometers from different manufacturers: both reliable, but not guaranteed to read identically.

International bodies including the College of American Pathologists have documented inter-laboratory variation in common IHC markers. This is expected, not a quality failure. Guidelines specify which assay and scoring system to use for each clinical decision, so oncologists interpret results in context rather than as universal figures.

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How can the same result look different in writing?

VariableOne way a lab might report itAnother way a different lab might report it
ER scoring methodER positive — Allred score 7 out of 8ER positive — high percentage of cells, strong intensity
HER2 borderline resultHER2: 2+ equivocal — reflex FISH recommendedHER2: 2+ borderline — proceed to ISH confirmation
PD-L1 clone documentedPD-L1 22C3 clone, TPS score reportedPD-L1 SP142 clone, IC score reported
Ki67 counting methodKi67: manual hot-spot countKi67: automated whole-slide image analysis

Which result should your oncologist use?

The result that matters is the one your oncologist knows about and has interpreted alongside the method used to generate it. A number without its context — the antibody clone, the scoring system, the laboratory's accreditation — cannot be acted on reliably.

Tell your oncologist if you have results from two different labs. They will compare the methods, not just the figures. Switching labs mid-treatment to chase a different number introduces uncertainty that is harder to manage than the original variation.

What else causes IHC variation between labs?

Why are PD-L1 results especially different between labs?

PD-L1 testing uses clones that were each validated in different contexts with different scoring methods. Some clones count only tumour cells; others include immune cells in the count. An oncologist needs to know not just the number but which clone produced it. ASCO and regulatory bodies have reviewed concordance data between the main clones in use and found that they do not always agree — which is why the clone name should appear on every PD-L1 report.

What does 'equivocal' mean on an HER2 report?

Equivocal means the IHC result sits in a borderline zone that does not clearly confirm or rule out protein overexpression. Most guidelines recommend a follow-on gene amplification test — ISH or FISH — before a final HER2 status is issued. Seeing 'equivocal' or '2+' on your report does not mean there is a problem. It means a second method is needed before the picture is complete, and your oncologist will arrange that.

Should we repeat the test at a different lab to be sure?

Repeating at a different lab rarely resolves uncertainty — it usually adds it, because the second lab will use different reagents producing a result that cannot be directly compared to the original. Situations where a repeat genuinely helps: the original sample was too small or poorly fixed, you want a second pathologist's interpretation of the same slides, or testing was never done at all. Ask your oncologist what specific question a repeat would answer before requesting one.

Does a higher number from a different lab mean my cancer is worse?

No. A higher number from a different assay means the two assays produced different measurements, which is expected and documented in the pathology literature. Your oncologist will not compare a new result from a different lab against an old result from your original lab as though they are equivalent units. What they look for is consistency within the same system over time — not comparisons across systems.

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Common questions

Frequently asked questions

My ER result was different at two labs. Which is correct?

Both may be correct relative to the assay each lab used. ER can be reported as an Allred score, an H-score, or a percentage of positive cells, and these are not directly comparable numbers. What your oncologist needs to know is how each lab scored the result and which assay they used. If both reports are clearly positive or clearly negative, the clinical conclusion is usually the same regardless of the specific figure.

My HER2 was 2+ at one lab and 3+ at another — how is that possible?

HER2 scoring at the boundary between 2+ and 3+ is the zone where variation is most common. The result depends on the intensity of staining across the cell membrane and the proportion of cells showing it, and different antibody clones differ in sensitivity at this boundary. Disagreement between labs on the same tissue in this range is documented in the pathology literature. Your oncologist will usually resolve it with a gene amplification test, which provides a more objective measure.

Does a lower Ki67 number from a different lab mean the tumour is less aggressive?

Not necessarily. Ki67 counting methods vary — hot-spot counting, mean field counting, and automated image analysis can all produce different numbers from the same slide. Your oncologist interprets Ki67 in the context of which laboratory performed it and which method they used. A difference in Ki67 between two labs tells you more about their respective methods than it tells you about a change in your tumour.

Should we get a second opinion on the same slides rather than a new test?

A second pathologist reviewing the same slides answers a different and often more useful question than ordering a new test on separate tissue. It asks whether the interpretation itself was accurate, rather than introducing a new variable. If you are uncertain about your results, ask your oncologist whether a second pathology opinion on the existing slides is appropriate. They can arrange this without a new biopsy.

What should I tell my oncologist when I bring results from two labs?

Bring the physical reports, not just the numbers. Each report should name the antibody clone, the scoring method, and the laboratory. Tell your oncologist the date of each test and the lab's name. If either report is missing the clone or scoring method, note that — your oncologist may need to contact the lab directly. The method is what makes the number meaningful.

Is IHC variation the same for all markers, or worse for some?

It varies by marker. PD-L1 is among the most variable because its clones were each validated in different contexts and score differently. Ki67 is also variable because counting methods differ significantly between labs. ER and PR testing has become more consistent since professional bodies including ASCO and CAP issued standardised protocols. Your oncologist knows which markers in your specific panel carry more or less uncertainty about comparability across labs.

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