Significance of HER2 protein expression and HER2 gene amplification in colorectal adenocarcinomas

Table 1 Clinicopathological features of colorectal cancers

Clinical / pathological features	n
Gender
Male	718
Female	477
Age (yr)
≤ 60	578
> 60	617
Tumor grade
G1	42
G2	857
G3	296
Tumor stage
pT1	32
pT2	175
pT3	937
pT4	51
Nodal status
pN0	593
pN1	296
pN2	306
Tumor type
Tubular carcinoma	1089
Mucinous carcinoma	106
Localization
Ascending colon	273
Transverse colon	32
Descending colon	56
Sigmoid	289
Rectum	545
Total number	1195

Table 2 Distribution of human epidermal growth factor receptor 2 staining in 1195 colorectal adenocarcinomas

Staining pattern	Number of cases	Positive rate
IHC 3+	31	2.6%
IHC 2+	105	8.8%
IHC 1+	475	39.7%
IHC 0	584	48.9%

IHC: Immunohistochemical staining.

Table 3 Concordance between human epidermal growth factor receptor 2 overexpression by Immunohistochemical staining and human epidermal growth factor receptor 2 gene amplification by fluorescence in situ hybridization

IHC score	HER2 gene amplification (FISH)		% HER2 gene amplification
	Positive	Negative
1+ (n = 10)	0	10	0%
2+ (n = 102)	12	90	11.8%
3+ (n = 29)	24	5	82.8%

HER2: Human epidermal growth factor receptor 2; FISH: Fluorescence in situ hybridization; IHC: Immunohistochemical staining.

Table 4 Association of human epidermal growth factor receptor 2 gene status with clinicopathological features n (%)

Clinicopathological features	HER2 status		P-value
	HER2 negative	HER2 positive
Gender			0.441
Male	616 (96.2)	24 (3.8)
Female	406 (97.1)	12 (2.9)
Age (yr)			0.272
≤ 60	501 (96.0)	21 (4.0)
> 60	521 (97.2)	15 (2.8)
Tumor grade			0.784
1	39 (97.5)	1 (2.5)
2	773 (96.7)	26 (3.3)
3	210 (95.9)	9 (4.1)
Histology			0.762
Tubular	937 (96.5)	34 (3.5)
Mucinous/other types	85 (97.7)	2 (2.3)
Tumor site			0.819
Colon	548 (96.5)	20 (3.5)
Rectal	474 (96.7)	16 (3.3)
Left-sided colon	203 (88.3)	27 (37.0)	0.514
Right-sided colon	292 (86.4)	46 (63.0)
Depth of invasion
T1	31 (100.0)	0 (0.0)	0.039
T2	165 (98.8)	2 (1.2)
T3	815 (96.3)	31 (3.7)
T4	11 (78.6)	3 (21.4)
T1-2	196 (99.0)	2 (1.0)	0.001
T3-4	826 (96.0)	34 (4.0)
Lymph node metastasis
N0	541 (96.3)	21 (3.7)	0.260
N1	261 (98.1)	5 (1.9)
N2	220 (95.7)	10 (4.3)
No	541 (96.3)	21 (3.7)	0.524
Yes	481 (97.0)	15 (3.0)
Distant metastasis			0.028
No	940 (96.9)	30 (3.1)
Yes	81 (92.0)	7 (8.0)
Tumor stage
(1)I-II	192 (98.5)	2 (1.0)	0.012
III	749 (96.5)	27 (3.5)
IV	81 (92.0)	7 (8.0)
(3)I-II	192 (99.0)	2 (1.0)	0.044
III-IV	830 (96.1)	34 (3.9)

HER2: Human epidermal growth factor receptor 2.

Table 5 Overall survival based on clinicopathological features

Clinicopathological features	Patients	Events	Median survival (95%CI), mo	P-value
Gender				0.707
Male	640	144	NA
Female	418	100	NA
Age (yr)
≤ 60	522	116	NA	0.591
> 60	536	128	NA
≤ 65	661	138	NA	0.027
> 65	397	106	NA
Tumor site				0.457
Colon	568	133	NA
Rectal	490	111	NA
Tumor grade				0.000
1-2	839	176	NA
3	219	68	NA
Histology				0.000
Tubular	971	205	NA
Mucinous/ Other types	87	39	54.90
Lymph node metastasis				0.000
No	562	61	NA
Yes	496	183	NA
Tumor stage				0.000
I-II	198	13	NA
III-IV	860	231	NA
HER2 protein overexpression by IHC
IHC (-)	935	221	NA	0.220
IHC (+)	123	23	NA
HER2 gene amplification by FISH
Positive	1022	234	NA	0.458
Negative	36	10	NA

NA: Because the overall survival rates of these patients were more than 50%, we didn’t get the median survival time. HER2: Human epidermal growth factor receptor 2; FISH: Fluorescence in situ hybridization; IHC: Immunohistochemical staining.