Serum HER2 as a predictive biomarker for tissue HER2 status and prognosis in patients with gastric cancer

Table 1 Clinicopathological characteristics

Variables	No. of patients	Percent
Age (range, 23-89, yr)
≥ 60	126	52.7
< 60	113	47.3
Gender
Male	167	69.9
Female	72	30.1
Smoking status
Never	61	25.5
Ever	178	74.5
Tumor location
GEJ	41	17.2
Non-GEJ	198	82.8
Tumor size
≥ 5 cm	102	42.7
< 5 cm	137	57.3
pTNM stage
I	39	16.3
II	78	32.6
III	102	42.7
IV	20	8.4
Lauren classification
Intestinal type	104	43.5
Diffuse type	135	56.5
Tissue HER2 status (IHC/FISH)
Positive	39	16.3
Negative	200	83.7
Serum HER2 ECD (ng/mL), median (range)	10.5 (4.2-190.2)

GEJ: Gastroesophageal junction; HER2: Human epidermal growth factor receptor-2; ECD: Extracellular domain; IHC: Immunohistochemistry; FISH: Fluorescence in situ hybridization.

Table 2 Diagnostic performance of serum HER2 extracellular domain for tissue HER2 status at different cut-off values

Cut-off values (ng/mL)	True positive	False positive	True negative	False negative	Sensitivity (95%CI)	Specificity (95%CI)
15.001	23	35	165	16	0.59 (0.42-0.74)	0.83 (0.77-0.88)
24.752	21	15	185	18	0.54 (0.37-0.70)	0.93 (0.88-0.96)

¹Value recommended by FDA for breast cancer;

²Value determined by Youden’s index in ROC plot.

Table 3 Association between clinicopathological variables and serum HER2 extracellular domain concentrations n (%)

Variables	Serum HER2 ECD concentrations		P value
	> 24.75 ng/mL (n = 36)	≤ 24.75 ng/mL (n = 203)
Age (yr)			0.474
≥ 60	17 (47.2)	109 (53.7)
< 60	19 (52.8)	94 (46.3)
Gender			0.396
Male	23 (63.9)	144 (70.9)
Female	13 (36.1)	59 (29.1)
Smoking status			0.452
Never	11 (30.6)	50 (24.6)
Ever	25 (69.4)	153 (75.4)
Tumor location			0.573
GEJ	5 (13.9)	36 (17.7)
Non-GEJ	31 (86.1)	167 (82.3)
Tumor size			< 0.001
≥ 5 cm	27 (75.0)	75 (36.9)
< 5 cm	9 (25.0)	128 (63.1)
Type of gastrectomy			0.266
Total	21 (58.3)	98 (48.3)
Subtotal	15 (41.7)	105 (51.7)
Type of surgery			0.730
Open	25 (69.4)	135 (66.5)
MIS	11 (30.6)	68 (33.5)
Lymph node involvement			0.419
Positive	22 (61.1)	138 (68.0)
Negative	14 (38.9)	65 (32.0)
pTNM stage			0.576
I	6 (16.7)	33 (16.3)
II	12 (33.3)	66 (32.5)
III	13 (36.1)	89 (43.8)
IV	5 (13.9)	15 (7.4)
Lauren classification			0.021
Intestinal type	22 (61.1)	82 (40.4)
Diffuse type	14 (38.9)	121 (59.6)
Tissue HER2 status (IHC/FISH)			< 0.001
Positive	21 (58.3)	18 (8.9)
Negative	15 (41.7)	185 (91.1)

GEJ: Gastroesophageal junction; HER2: Human epidermal growth factor receptor-2; ECD: Extracellular domain; MIS: Minimally invasive surgery; IHC: Immunohistochemistry; FISH: Fluorescence in situ hybridization.