9
Figure 3. Evaluation of HER2 Gene Amplification by ISH
Assay of the Invasive Component of a Breast
Cancer Specimen Using a Dual-signal (HER2 gene)
Assay (Dual-probe ISH)
HER2 testing (invasive component)
by validated dual-probe ISH assay
Batch controls and on-slide controls
show appropriate hybridization
HER2/CEP17 ratio
≥2.0
"Group 3"
Average HER2
copy number
≥6.0 signals/cell
HER2/CEP17 ratio
<2.0
"Group 4"
Average HER2 copy
number ≥4.0 and
<6.0 signals/cell
Additional
Workup required.
See Fig 4.
NOTE. e final reported results assume that there is no apparent histopathologic discordance
observed by the pathologist. Regarding Groups 2, 3, and 4, if not already assessed by the institution/
lab performing the ISH test, IHC testing for HER2 should be performed using sections from the
same tissue sample used for ISH and the slides from both ISH and IHC be reviewed together to guide
the selection of areas to score by ISH(local practice considerations will dictate the best procedure to
accomplish this concomitant assessment).
"Group 5"
Average HER2
copy number
<4.0 signals/cell
"Group 1"
Average HER2
copy number ≥4.0
signals/cell
"Group 2"
Average HER2
copy number
<4.0 signals/cell
ISH
positive
Additional
Workup
required.
See Fig 5.
Additional
Workup
required.
See Fig 6.
ISH
negative
