HER2 heterogeneity is a poor prognosticator for HER2-positive gastric cancer

Table 1 Patients’ demographic information

	Homo, n = 65	Hetero, n = 23	P-value
Age in yr	69 (42-81)	67.0 (45-82)
< 70	34 (52%)	15 (65%)	0.284
≥ 70	31 (48%)	8 (35%)
Sex
Male	43 (66%)	18 (78%)	0.279
Female	22 (34%)	5 (22%)
ECOG performance status
0	61 (94%)	20 (87%)	0.152
1	2 (3%)	3 (13%)	(0 vs ≥ 1)
2	2 (3%)	0
Macroscopic type
1	7 (11%)	1 (5%)	0.008
2	28 (43%)	4 (17%)	(type 1/2 vs 3/4)
3	23 (35%)	16 (69%)
4	7 (11%)	2 (9%)
Tumor location
Upper	27 (42%)	11 (48%)	0.601
Middle / lower	38 (58%)	12 (52%)
Histology
Well differentiated	48 (74%)	14 (61%)	0.31
Poorly differentiated	15 (23%)	9 (39%)
Other/unknown	2 (3%)	0
T status
cT2	2 (3%)	0	0.267
cT3	17 (26%)	4 (17%)	(cT2/3 vs cT4)
cT4	46 (71%)	19 (83%)
N status
cN0	5 (8%)	2 (9%)	0.748
cN1	5 (8%)	1 (4%)	(≤cN2 vs cN3)
cN2	32 (49%)	11 (48%)
cN3	23 (35%)	9 (39%)
Number of non-curative factor
0	1 (1%)	1 (4%)	0.404
1	32 (49%)	13 (57%)	(≤1 vs >1)
2	29 (45%)	9 (39%)
>2	3 (5%)	0
Non-curative factor
Lymph node	34 (52%)	10 (43%)
Peritoneal	22 (34%)	6 (26%)
Hepatic	27 (42%)	12 (52%)
Other	9 (14%)	1 (5%)
Number of HER2 assessment
2	35 (54%)	10 (43%)	0.393
3	27 (42%)	13 (57%)
>3	3 (4%)	0
HER2 score
3+	53 (82%)	10 (43%)	0.001
2+	12 (18%)	13 (57%)
Upfront chemotherapy
SOXT	33 (50%)	12 (52%)
XPT	25 (37%)	7 (30%)
SPT	3 (5%)	2 (9%)
FPT	1 (2%)	2 (9%)
FLT	1 (2%)
PTXT	1 (2%)
DCST	1 (2%)

ECOG: Eastern Cooperative Oncology Group; SOXT: S-1 oxaliplatin capecitabine trastuzumab; XPT: capecitabine cisplatin trastuzumab; SPT: S-1 cisplatin trastuzumab; FPT: 5-Fluorouracil cisplatin trastuzumab; FLT: 5-Fluorouracil leucovorin trastuzumab; PTXT: Paclitaxel trastuzumab; DCST: Docetaxel cisplatin S-1 trastuzumab.

Table 2 Prognostic factors for overall survival and progression-free survival

Covariates	Overall survival				Progression-free survival
	Univariate analysis		Multivariable analysis		Univariate analysis		Multivariable analysis
	HR (95%CI)	P-value	HR (95%CI)	P-value	HR (95%CI)	P-value	HR (95%CI)	P-value
Age, ≥ 80 vs < 80	1.31 (0.473-3.625)	0.604			1.138 (0.492-2.633)	0.762
Sex, female vs male	1.057 (0.621-1.798)	0.838			1.005 (0.615-1.642)	0.985
Macroscopic type, type 3,4 vs 1,2	1.72 (1.027-2.881)	0.039			1.641 (1.037-2.598)	0.034
Clinical tumor depth, cT4 vs ≤ cT3	1.838(0.992-3.405)	0.053			1.408 (0.826-2.401)	0.209
Clinical nodal status, cN3 vs ≤ cN2	2.026 (1.184-3.466)	0.01	2.119 (1.165-3.855)	0.014	1.691 (1.056-2.708)	0.029	1.622 (0.951-2.764)	0.076
Histology, undiff. vs diff.	1.884 (1.090-3.255)	0.023	2.612 (1.388-4.916)	0.003	1.643 (1.031-2.618)	0.037	1.902 (1.117-3.237)	0.018
HER2 score, 2+ vs 3+	2.331 (1.353-4.016)	0.002	2.008 (1.094-3.690)	0.024	1.828 (1.110-3.012)	0.018	1.612 (0.940-2.770)	0.083
HER2 heterogeneity, hetero vs homo	2.439 (1.389-4.274)	0.002	3.115 (1.610-6.024)	0.001	2 (1.203-3.333)	0.008	2.123 (1.225-3.676)	0.007
No. of non-curative factors, ≥ 2 vs 1	1.904 (1.138-3.186)	0.014	2.252 (1.113-4.553)	0.024	1.875 (1.185-2.965)	0.007	1.871 (1.023-3.424)	0.042
M1, lymph node	0.687 (0.410-1.150)	0.154			0.568 (0.358-0.902)	0.017
M1, peritoneal	1.207 (0.699-2.086)	0.5			1.327 (0.828-2.127)	0.24
M1, hepatic	1.902 (1.141-3.173)	0.014	2.084 (1.076-4.036)	0.029	1.974 (1.244-3.132)	0.004	2.053 (1.151-3.664)	0.015

HER2: Human epidermal growth factor receptor 2; HR: Hazard ratio.