12
Optimal Algorithm
Figure 6. Clinical Question 5 "Group 4"
HER2/CEP17 ratio<2.0
Average HER2 signals/cell ≥4.0 and <6.0
Assess IHC using sections from the
same tissue sample used for ISH
IHC 0/1+
HER2/CEP17 ratio <2.0
Average HER2 signals/cell
≥4.0 and <6.0
IHC 3+
HER2 Negative
with Comment
a
a
Comment: It is uncertain whether patients with ≥4.0 and <6.0 average HER2 signals/cell and
HER2/CEP17 ratio <2.0 benefit from HER2 targeted therapy in the absence of protein over
expression (IHC3+). If the specimentest result is close to the ISH ratio threshold for positive, there
is a higher likelihood that repeat testing will result in different results by chance alone. erefore,
when IHC results are not 3+ positive, it is recommended that the sample be considered HER2
negative without additional testing on the same specimen.
Other ISH Result
Observer blinded to previous
results recounts ISH,
counting at least 20 cells
Result should be
adjudicated per
internal procedures
to determine final
category
IHC 2+
HER2 Positive
HER2
Negative with
Comment
a
