HERACLES Diagnostic Criteria for HER2 (ERBB2) Scoring of a Colorectal Cancer

The HERACLES trial used diagnostic criteria for the testing to detect overexpression of HER2 (ERBB2, neu) in immunohistochemistry (IHC).

Patient selection: colorectal adenocarcinoma

Parameters:

(1) degree of staining of tumor cells

(2) pattern of staining

(3) percentage of cells staining

Degree of Staining	Pattern of Staining	Percentage	Classification
none	NA	NA	negative
faint (1+)	segmental or granular	NA	negative
moderate (2+)	circumferential, basolateral, lateral	< 50%	negative
moderate (2+)	circumferential, basolateral, lateral	>= 50%	equivocal
intense (3+)	circumferential, basolateral, lateral	<= 10%	negative
intense (3+)	circumferential, basolateral, lateral	11 to 49%	positive
intense (3+)	circumferential, basolateral, lateral	>= 50%	positive

Classification	In situ hybridization
negative	no
equivocal	repeat IHC; if still >= 50% then in situ hybridization
positive, 11 to 49%	repeat IHC; if still > 10% then in situ hybridization
positive, > 50%	in situ hybridization recommended but not required

In situ hybridization is considered amplified if the ERBB2 to CEP17 ratio is >= 2 in >= 50% of cells.

Anti-HER2 therapy is only indicated if all of the following:

(1) HER2-amplified on ISH or strongly positive on ICH

(2) RAS wild type

(3) BRAF wild type

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