A systematic review and meta-analysis for human epidermal growth factor receptor 2 on upper tract urothelial carcinoma patients

Objective: The expression and significance of human epidermal growth factor receptor 2 (Her2) in upper tract urothelial carcinoma (UTUC) remains controversial. Thus, we aimed to systemically review the Her2 expression in UTUC patients and its relationship with pathological characters and clinical outcomes with meta-analysis. Materials and methods: A systematically computerized search in PubMed, Scopus, Embase and Cochrane was conducted. From a total of 454 related articles, 35 articles were finally reviewed and 16 papers were chosen for further analysis. Pathological characters included tumor stage, grade, lymph node metastasis (LNM) and lymphovascular invasion (LVI). The clinical outcomes included overall survival (OS), recurrence-free survival (RFS), cancer specific survival (CSS), metastatic-free survival (MFS) and progression-free survival (PFS). RevMan software was used for meta-analyses. Results: In total 16 studies from 1994 to 2020 were chosen, 14 studies used immunohistochemistry to assess the expression of Her2 and 5 studies used in situ hybridization, with a positive rate of 0 to 74.0% and 7.2 to 18.1%, respectively. Her2-positive was significantly associated with stage (pooled HR 1.86; 95 % CI 1.43–2.42), grade (pooled HR 2.81; 95 % CI 1.01–7.85) and LNM (pooled HR 1.93; 95 % CI 1.18–3.15). However, there was no statistically relationship between Her2-positive with LVI (pooled HR 1.48; 95 % CI 0.64–3.46) and RFS (pooled HR 1.41; 95 % CI 0.98–1.83). Conclusions: This review indicated that UTUC patients with Her2-positive tended to develop higher stage and grade tumors and LNM. The Her2 expression in UTUC patients deserves further investigation in the future.