Published online Oct 24, 2025. doi: 10.5306/wjco.v16.i10.110047
Revised: July 15, 2025
Accepted: September 25, 2025
Published online: October 24, 2025
Processing time: 140 Days and 19.6 Hours
Human epidermal growth factor receptor 2 (HER2) plays pivotal roles in cellular proliferation, survival, and differentiation of several malignancies. Upper tract urothelial carcinoma (UTUC) is a relatively rare malignancy. The clinical and molecular significance of HER2 expression level in UTUC remains poorly characterized vs bladder cancer.
To comprehensively evaluate HER2 expression patterns and their association with UTUC patients’ clinicopathological features.
Data were retrospectively collected from patients diagnosed with UTUC at The First Affiliated Hospital of Guangxi Medical University between January 2023 and December 2024. HER2 status was evaluated by immunohistochemistry in 145 UTUC patients who met the inclusion criteria. Its associations with tumor grade, tumor stage, and other clinicopathological parameters were assessed. The χ2 test or Fisher’s exact test, along with univariate and multivariate logistic regression analyses, were performed to determine the influences of clinicopathological factors on HER2 expression.
HER2 positivity was significantly associated with high tumor grade (P = 0.003), while other variables, including sex, anatomical tumor location, pathological T stage, Ki-67 proliferation index, nodal metastasis status, lymphovascular invasion, and tumor laterality failed to demonstrate statistically significant correlations. These findings were further substantiated through univariate logistic regression modeling, yielding an odds ratio of 3.56 [95% confidence interval (CI): 1.30-9.75; P = 0.013] for the association between high tumor grade and HER2 positivity. Importantly, this relationship remained robust (hazard ratio = 3.42, 95%CI: 1.22-9.60; P = 0.019) even after implementing multivariate logistic regression analysis. With a median follow-up time of 8 months (interquartile range, 4-14) months, 14 patients experienced intravesical recurrence after radical nephroureterectomy. Certain patient characteristics, such as HER2-negative, male sex, high-grade tumors, and luminal phenotype, were associated with a higher risk of intravesical recurrence.
In UTUC, HER2 overexpression is closely associated with tumor dedifferentiation (high grade), while it does not correlate with conventional indicators of disease progression, indicating that HER2 may serve a distinct biological function in this cancer type.
Core Tip: This is a retrospective single-center observational study to evaluate human epidermal growth factor receptor 2 (HER2) expression patterns by immunohistochemistry in 145 upper tract urothelial carcinoma (UTUC) specimens and assessed its correlation with tumor grade, stage, molecular subtype, and other clinicopathological parameters. HER2 overexpression in UTUC is strongly linked to tumor dedifferentiation (high grade), while other variables including sex, anatomical tumor location, pathological T stage, Ki-67 proliferation index, nodal metastasis status, lymphovascular invasion, and tumor laterality all failed to demonstrate statistically meaningful correlations. This distinct pattern suggests HER2 may play a unique biological role in UTUC compared to other epithelial malignancies.