What Does IHC 0, 1+, 2+, or 3+ Mean?

This page is for people whose pathology report shows an IHC score such as 0, 1+, 2+, or 3+. It explains what the score measures, why it means different things for different markers, and what to ask.

Immunohistochemistry, usually shortened to IHC, is a stain. A pathologist applies an antibody to a slice of your tumor. The antibody sticks to one specific protein and drags a color with it. Under the microscope, the pathologist then judges two things: how dark the color is, and how many tumor cells show it.

The 0, 1+, 2+, 3+ scale is that judgment written down. Zero means no staining. Three plus is the strongest score.

It is a visual grading scale read by a human being. That fact explains most of what follows.

There is no universal meaning to "2+." The cutoffs are written separately for each protein, in each cancer type, by guideline committees. A 2+ for one marker can be a firm result. For another it means the test has failed to decide.

So the first question about any IHC score is never "is 2+ good or bad." It is "2+ of what, in what cancer."

HER2 is a growth-signaling protein on the cell surface. Too much of it drives faster growth, and it is also a drug target.

The National Cancer Institute's clinician summary sets out the ASCO/CAP thresholds:

• IHC 0 or 1+ — negative
• IHC 2+ — equivocal, meaning undecided
• IHC 3+ — positive

Your team uses the result, with other tests, to plan treatment.

This is the most useful thing to know about the scale. NCI states that an equivocal 2+ requires an alternative in situ hybridization test to resolve it. In situ hybridization, or ISH, counts actual copies of the HER2 gene instead of judging stain color.

NCI gives the dual-probe ISH thresholds it uses:

• Negative — HER2/CEP17 ratio below 2.0 and HER2 copy number below 4
• Equivocal — ratio below 2.0 and copy number of 4 or more but under 6
• Positive — ratio of 2.0 or more, or copy number of 6 or more

CEP17 is a reference marker on chromosome 17. The ratio compares HER2 copies against it, which corrects for tumors carrying extra whole chromosomes.

If your report says 2+ and nothing else, the answer is still pending. Ask whether ISH was ordered and when it results.

Older reports often filed IHC 1+ as simply negative. Newer terms such as "HER2-low" are now used for some breast cancers with lower HER2 scores, and some treatments are studied or approved for them. I could not open the FDA approval page for this check, so this page does not give drug names or trial numbers. Ask your team whether your score, and the second test if you had one, affects your treatment options. See HER2-Low Breast Cancer.

Estrogen receptor and progesterone receptor are also read by IHC, but the answer is a percentage, not a plus sign.

NCI gives one threshold for both. Any staining in 1% of cells or more is considered positive.

So a report reading "ER 90%, PR 5%, HER2 1+" is mixing two different scoring systems in one line. Read each on its own terms.

A third pattern shows up in colorectal, endometrial, and other cancers. Mismatch repair (MMR) proteins are stained, and the result is reported by whether the proteins are expressed, not by a 0 to 3+ grade.

NCI's colorectal cancer genetics summary says tumor evaluation for Lynch syndrome, an inherited condition that raises cancer risk, often begins with IHC for MMR protein expression or microsatellite instability (MSI) testing, BRAF testing, and MLH1 hypermethylation analysis.

That is why a "loss of MLH1" line is not the end of the workup. It is the beginning of one.

IHC is read by a person, and a borderline score is a judgment call. If your result is borderline or does not fit the clinical picture, you can ask:

• Which antibody clone and scoring guideline the lab used
• Whether the score came from the biopsy, the surgical specimen, or both
• Whether a spread site has been tested
• Whether the slides can be sent for outside review

• Which protein was stained, and what score did it get?
• Is that score positive, negative, or equivocal for this specific cancer?
• If it is equivocal, what confirmatory test was ordered and when is it back?
• Does this score change which treatments or trials I can consider?
• Was this tested on the original tumor or on a newer sample?

HER2-Low Breast Cancer covers that category in depth. MSI-H Colorectal Cancer and dMMR Endometrial Cancer follow the mismatch repair path. Pathology Reports explains the rest of the document these scores sit in.

• NCI PDQ — Breast Cancer Treatment (Health Professional Version)
• NCI PDQ — Genetics of Colorectal Cancer (Health Professional Version)