7
Figure 1. Evaluation of HER2 Protein Expression by IHC
Assay of the Invasive Component of a Breast
Cancer Specimen
HER2 Testing (invasive component)
by Validated IHC Assay
IHC 3+
positive
Batch controls and on slide controls
show appropriate staining
Circumferential
membrane staining that
is complete, intense
and within >10% of
tumor cells
a
Weak to moderate
complete membrane
staining observed in
>10% of tumor cells
Incomplete membrane
stainingthat is faint/barely
perceptible and within
>10% of tumor cells
No staining is observed
or
Membrane staining that
is incomplete and is faint/
barely perceptible and
within ≤10% of tumor cells
IHC 2+
equivocal
IHC 1+
negative
IHC 0
negative
Must order reflex test (same specimen using ISH) or order a
new test (new specimen if available, using IHC or ISH)
(Strong Recommendation; EB-H)
NOTE. e final reported results assume that there is no apparent histopathologic discordance
observed by the pathologist. Unusual staining patterns of HER2 by IHC can be encountered that
are not covered by these definitions. In practice, these patterns are rare and if encountered should
be considered IHC2+ equivocal. As one example, some specific subtypesof breast cancers can show
IHC staining that is moderate to intense but incomplete (basolateral or lateral) and can be found to
be HER2 amplified. Another example is circumferential membrane IHC staining that is intense but
within ≤10% of tumor cells (heterogeneous but very limited in extent). Such cases can be considered
2+ equivocal but additional samples may reveal different percentages of HER2 positive staining.
a
Readily appreciated using a low power objective and observed within a homogeneous and
contiguous invasive cell population.
Optimal Algorithm
