HER2 testing in gastric cancer: An update

Table 1 Advantages and disadvantages of the human epidermal growth factor receptor 2 testing methods

Method	Advantages	Disadvantages
IHC	Quick to perform;	Equivocal cases (2+) need another method for conclusion;
	Most laboratories use fully automated processes;	Accuracy is more dependent on pre-analytic variables
	Widely used and familiar to all pathologists;
	Results can be viewed using a conventional bright-field microscope;
	Permits parallel viewing of tumor cell morphological features;
	Stained tissues do not degrade over time
FISH	Very objective and accurate;	Technically more demanding;
	Actual copies of HER2 genes can be counted;	Usually performed only in large laboratories/institutions;
	Considered the golden standard of HER2 testing	Costs are substantially high;
		Requires the use of fluorescence microscope and dark room;
		Comparatively more time consuming;
		Reagents degrade over time
SISH/CISH/DDISH	Quick to perform;	More expensive than IHC;
	Very objective and accurate;	Unfamiliar to non-specialist pathologists
	Technique is fully automated;
	Results can be viewed using a conventional bright-field microscope;
	Permits parallel viewing of tumor cell morphological features;
	Slides can be stored because the signal is stable;
	Double-stranded probes labeled with two haptens can detect both markers on a single slide (DDISH)

IHC: Immunohistochemistry; FISH: Fluorescent in situ hybridization; SISH: Silver in situ hybridization; CISH: Chromogenic in situ hybridization; DDISH: Dual-color dual-hapten in situ hybridization.

Table 2 Immunohistochemistry scoring for human epidermal growth factor receptor 2 expression in gastric and gastroesophageal junction cancer[17]

Score	Surgical specimen	Biopsy	HER2 overexpression assessment
0	No membranous staining or staining of < 10% of the tumor cells	No membranous staining or staining only in rare cells (less than 5 cohesive cells)	Negative
1+	Staining is weak or detected in only one part of the membrane in ≥ 10% of the cells	Staining is weak or detected in only one part of the membrane of at least 5 cohesive cells	Negative
2+	Moderate/weak complete or basolateral membranous staining in ≥ 10% of the cells	Moderate/weak complete or basolateral membranous staining of at least 5 cohesive cells	Equivocal
3+	Strong complete or basolateral membranous staining in ≥ 10% of the neoplastic cells	Strong complete or basolateral membranous staining of at least 5 cohesive cells	Positive

HER2: Human epidermal growth factor receptor 2.