Correlation of HER2 expression and clinicopathological characteristics in patients with urothelial carcinoma in China

doi:10.19401/j.cnki.1007-3639.2024.11.003

Abstract

Abstract:

Background and purpose: Human epidermal growth factor receptor 2 (HER2) is closely associated with drug efficacy and prognosis in urothelial carcinoma (UC). HER2 is a significant biomarker and therapeutic target in various tumors. In recent years, anti-HER2 antibody-drug conjugates have shown significant clinical efficacy in UC patients with HER2 overexpression. Therefore, an in-depth understanding of HER2 expression and its characteristics in Chinese UC patients is crucial to guide treatment decision-making, optimize treatment strategies and achieve personalized therapy. This study aimed to thoroughly investigate correlation of HER2 expression and clinicopathological characteristics in Chinese patients with UC. Methods: This study was a multicenter study that retrospectively included UC patients from urology departments of 8 tertiary hospitals in 5 geographical regions of China (North China, East China, South China, Central China and Northwest) whose tissue samples were collected from January 2023 to March 2024. Inclusion criteria: ① age above 18 years; ② UC diagnosed by histopathological or cytological examination; ③ complete results of HER2 expression detection using immunohistochemistry (IHC) in the primary tumor site were required. Exclusion criteria: ① diagnosed patients with tumors in other parts of the body; ② physicians evaluated other situations that were not suitable for inclusion in this study. IHC results for HER2 expression and clinicopathological data were collected. HER2 expression was determined according to the criteria outlined in “Clinical pathological expert consensus on HER2 testing in urothelial carcinoma in China”, with HER2 2＋ and 3＋ defined as HER2 overexpression. The HER2 expression and clinicopathological features were analyzed. This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center (ethical number: 2301268-12) and was registered at China Clinical Trial Registry (registration number: ChiCTR2300069746). Results: A total of 1054 patients with UC were included. Most of the tumors were bladder UC (n=807, 76.6%). The mean age of patients was (66.8±10.5) years, and the majority were male (78.5%). The HER2 overexpression rate was 58.4% (n=616), with an additional 23% of patients having HER2 1＋ expression (n=242), and a small proportion exhibiting negative HER2 expression (n=196, 18.6%). HER2 expression was significantly associated with various clinical and pathological characteristics such as Eastern Cooperative Oncology Group (ECOG) performance status, history of cardiovascular disease, history of metabolic disorders, smoking, UC disease location, differentiation grade, pathological type, and tumor stage. Conclusion: Retrospective analysis of multi-center data shows that HER2 expression is frequently observed in Chinese UC patients, with an overexpression rate of up to 58.4%. Furthermore, HER2 expression is closely associated with various clinical and pathological features of UC patients. This study underscores the critical importance of accurately assessing HER2 expression in UC patient to guide personalized therapies.

Key words: Urothelial carcinoma, Human epidermal growth factor receptor 2, Clinicopathological characteristics, China

CLC Number:

R737.1

WANG Shanshan, YE Dingwei, YANG Li, CHENG Fan, YANG Tiejun, ZHANG Xiaoping, YU Zhixian, ZHANG Qingyun, YANG Yong. Correlation of HER2 expression and clinicopathological characteristics in patients with urothelial carcinoma in China[J]. China Oncology, 2024, 34(11): 1011-1019.

Figures/Tables 5

Tab. 1

Tab. 2

Relationship between HER2 expression in primary lesions and clinicopathological characteristics in patients with UC"

Characteristic	Number of patients (n=1 054)	HER2 IHC 0 (n=196)	HER2 IHC 1＋(n=242)	HER2 IHC 2＋/3＋ (n=616)	Proportion of HER2 over-expression in subgroups percentage (95% CI)	Inter-subgroup difference (Wilcoxon Z value)	P value
Age/year						4.659	0.097
<60	243	54	61	128	52.7% (46.4%, 59.0%)
≥60	811	142	181	488	60.2% (56.8%, 63.6%)
Gender						3.504	0.173
Male	827	146	186	495	59.9% (56.6%, 63.2%)
Female	227	50	56	121	53.3% (46.8%, 59.8%)
ECOG						15.774	<0.001
0	323	47	59	217	67.2% (62.1%, 72.3%)
1	395	84	103	208	52.7% (47.8%, 57.6%)
2	33	9	7	17	51.5% (34.4%, 68.6%)
3	2	0	1	1	50.0% (0.0%, 100.0%)
Missing	301	56	72	173	57.5% (51.9%, 63.1%)
Hypertension						0.056	0.972
No	622	116	146	360	57.9% (54.0%, 61.8%)
Yes	427	79	96	252	59.0% (54.3%, 63.7%)
Diabetes mellitus						0.504	0.777
No	863	160	200	503	58.3% (55.0%, 61.6%)
Yes	181	35	42	104	57.5% (50.3%, 64.7%)
Cardiovascular and cerebrovascular diseases						7.012	0.030
No	874	175	198	501	57.3% (54.0%, 60.6%)
Yes	168	19	44	105	62.5% (55.2%, 69.8%)
Lipid metabolism disorders						10.175	0.006
No	1019	191	235	593	58.2% (55.2%, 61.2%)
Yes	17	3	7	7	41.2% (17.8%, 64.6%)
Other medical history						1.849	0.397
No	683	130	148	405	59.3% (55.6%, 63.0%)
Yes	371	66	94	211	56.9% (51.9%, 61.9%)
Smoking history						11.138	0.004
No	786	164	180	442	56.2% (52.7%, 59.7%)
Yes	268	32	62	174	64.9% (59.2%, 70.6%)
Alcohol consumption						1.812	0.404
No	917	175	213	529	57.7% (54.5%, 60.9%)
Yes	137	21	29	87	63.5% (55.4%, 71.6%)
Pathological type						16.491	<0.001
Non-invasive	406	66	120	220	54.2% (49.4%, 59.0%)
Invasive	648	130	122	396	61.1% (57.3%, 64.9%)
Differentiation grade						31.921	<0.001
Well-differentiated	141	45	51	45	31.9% (24.2%, 39.6%)
Moderately differentiated	118	14	32	72	61.0% (52.2%, 69.8%)
Poorly differentiated	795	137	159	499	62.8% (59.4%, 66.2%)
Disease type						36.980	<0.001
Bladder UC	807	122	176	509	63.1% (59.8%, 66.4%)
Upper urinary tract UC	247	74	66	107	43.3% (37.1%, 49.5%)
Upper urinary tract UC stage						12.019	0.002
0a	15	4	8	3	20.0% (0.0%, 40.2%)
0is	13	6	5	2	15.4% (0.0%, 35.0%)
Ⅰ	55	18	13	24	43.6% (30.5%, 56.7%)
Ⅱ	96	32	29	35	36.5% (26.9%, 46.1%)
Ⅲ	37	7	4	26	70.3% (55.6%, 85.0%)
Ⅳ	31	7	7	17	54.8% (37.3%, 72.3%)
Bladder UC stage						11.943	0.003
0a	109	20	38	51	46.8% (37.4%, 56.2%)
0is	83	20	26	37	44.6% (33.9%, 55.3%)
Ⅰ	311	26	59	226	72.7% (67.7%, 77.7%)
Ⅱ	170	25	27	118	69.4% (62.5%, 76.3%)
ⅢA	82	17	14	51	62.2% (51.7%, 72.7%)
ⅢB	24	9	7	8	33.3% (14.4%, 52.2%)
ⅢC	1	0	0	1	100.0% (100.0%, 100.0%)
ⅣA	19	4	4	11	57.9% (35.7%, 80.1%)
ⅣB	5	1	1	3	60.0% (17.1%, 102.9%)
Metastasis						1.102	0.576
No	993	180	229	584	58.8% (55.7%, 61.9%)
Yes	50	12	11	27	54.0% (40.2%, 67.8%)
Surgical treatment						2.796	0.247
No	30	9	5	16	53.3% (35.4%, 71.2%)
Yes	1021	187	236	598	58.6% (55.6%, 61.6%)

Tab. 2

Fig. 1

Fig. 2

Tab. 3

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IHC staining patterns	Score criteria
No staining or <10% invasive cancer cells with incomplete and weak membrane staining	0
≥10% invasive cancer cells with incomplete and weak membrane staining	1＋
≥10% invasive cancer cells with weak to moderate intensity and complete membrane staining, or <10% invasive cancer cells with strong and complete membrane staining	2＋
≥10% invasive cancer cells with strong and complete membrane staining	3＋