Role of human epidermal growth factor receptor 2 in gastric cancer: Biological and pharmacological aspects

Table 1 Interpretation and scoring of human epidermal growth factor receptor 2 immunohistochemistry for gastric cancer, as approved by the United States Food and Drug Administration in relation to the HercepTest (Dako)

Score	Surgical specimen staining pattern	Biopsy specimen staining pattern	HER2 overexpression assessment
0	No reactivity or membranous reactivityin < 10% of tumor cells	No reactivity or no membranous reactivity in any (or < 5 clustered) tumor cells	Negative
1+	Faint/barely perceptible membranous reactivity in ≥ 10% of tumor cells; cells are reactive only in part of their membrane	Tumor cell cluster (≥ 5 cells) with a faint/barely perceptible membranous reactivity irrespective of percentage of tumor cells stained	Negative
2+	Weak to moderate complete, basolateral or lateral membranous reactivity in ≥ 10% of tumor cells	Tumor cell cluster (≥ 5 cells) with a weak to moderate complete, basolateral, or lateral membranous reactivity irrespective of percentage of tumor cells stained	Equivocal
3+	Strong complete, basolateral or lateral membranous reactivity in ≥ 10% of tumor cells	Tumor cell cluster (≥ 5 cells) with a strong complete, basolateral, or lateral membranous reactivity irrespective of percentage of tumor cells stained	Positive

HER2: Human epidermal growth factor receptor 2.

Table 2 Positive human epidermal growth factor receptor 2 status by immunohistochemistry and/or fluorescence in situ hybridization for the patients enrolled in the ToGA trial[10,11,27]

HER2 status	n
IHC0/FISH+	61
IHC1+/FISH+	70
IHC2+ FISH+	159
IHC3+/FISH+	256
IHC3+/FISH-	15
IHC3+/FISH no results	16
IHC no results/FISH+	7
Total	584

N: Number of patients. HER2: Human epidermal growth factor receptor 2; IHC: Immunohistochemistry; FISH: Fluorescence in situ hybridization.

Table 3 Overview of the phase II and III compounds and their targets

Compounds	Type of compound	Target(s)	Clinical phase
Dacomitinib (PF-00299804, Pfizer)	Irreversible pan-HER TKI	HER1 (EGFR) and HER2	II
Afatinib (Gilotrif, Boehringer Ingelheim)	Irreversible pan-HER TKI	HER1 (EGFR), HER2, and HER4	II
Pertuzumab (Perjeta, Roche/Genentech)	mAb	HER2 (subdomain II), HER2 hetero dimerization	II/III
Ado-trastuzumab emtansine (Kadcyla, Roche/Genentech)	ADC	HER2 (subdomain IV)	II/III
Lapatinib (Tyverb/Tykerb, GSK)	Reversible pan-HER TKI	HER1 (EGFR) and HER2	III

TKI: Tyrosine kinase inhibitors; mAb: Monoclonal antibody; ADC: Antibody-drug conjugate.