3
➤ If a case has an average of ≥6.0 HER2 signals/cell with a HER2/
CEP17 Ratio of <2.0, formerly diagnosed as ISH Positive for HER2,
a definitive diagnosis will be rendered based on additional workup.
(Strong Recommendation; EB-I)
• 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 review):
a. If the IHC result is 3+, diagnosis is HER2 POSITIVE
b. If the IHC result is 2+, recount ISH by having an additional observer, blinded
to previous ISH results, count at least 20 cells that include the area of invasive
cancer with IHC 2+ staining :
▶ If reviewing the count by the additional observer changes the result into
another ISH category, the result should be adjudicated per internal
procedures to define the final category.
▶ If the HER2/CEP17 ratio remains <2.0 with ≥6.0 HER2 signals/cell, the
diagnosis is HER2 POSITIVE.*
c. If the IHC result is 0/1+, diagnosis is HER2 NEGATIVE with a comment.*
*Note: Refer to full text guideline for the specific comments associated with
each recommendation.
➤ If the case has an average HER2 signals/tumor cell of ≥4.0 and <6.0
HER2 signals/cell and HER2/CEP17 Ratio is <2.0, formerly diagnosed as
ISH Equivocal for HER2, a definitive diagnosis will be rendered based on
additional workup. (Strong Recommendation; EB-I)
• 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 review):
a. If the IHC result is 3+, diagnosis is HER2 POSITIVE
b. If the IHC result is 2+, recount ISH by having an additional observer, blinded
to previous ISH results, count at least 20 cells that include the area of invasive
cancer with IHC 2+:
▶ If reviewing the count by the additional observer changes the result into
another ISH category, the result should be adjudicated per internal
procedures to define the final category.
▶ If the count remains an average of ≥4.0 and <6.0 HER2 signals/cell with
HER2/CEP17 ratio <2.0, the diagnosis is HER2 NEGATIVE with a
comment.*
c. If the IHC result is 0/1+, diagnosis is HER2 NEGATIVE with a comment.*
*Note: Refer to full text guideline for the specific comments associated with
each recommendation.
Highlights
