Work

An Evaluation of HER2 Expression Heterogeneity in Primary Tumors and Metastatic Lymph Nodes of Patients With Advanced Extramammary Paget's Disease: Prognostic and Therapeutic Implications

Year: 2025

Type: article

Abstract: BACKGROUND: HER2 expression in primary versus metastatic tumors in advanced Extramammary Paget's Disease (EMPD) remains inadequately characterized. This investigation aimed to assess HER2 expression heterogeneity between primary tumors and metastatic lymph nodes (LNs) in patients with advanced EMPD and to assess the prognostic value of HER2 expression and other pathological factors in determining the therapeutic value of HER2 targeting. METHODS: We included 170 patients diagnosed with primary EMPD. Survival outcomes were analyzed using multivariate Cox regression and log-rank analysis, while inconsistencies in HER2 expression between primary and metastatic LNs were assessed using the kappa coefficient. RESULTS: HER2 high-expression was observed in 71.6% of primary tumors and 68.8% of metastatic LNs, with high HER2 expression correlating with poorer overall survival. Multivariate Cox analysis identified advanced N stage and HER2 high-expression in primary tumors as independent poor prognostic factors. In 31 paired samples, the discordance rate of HER2 status between primary tumors and corresponding LNs was 35.48% (n = 11) (Kappa 0.11, 95% CI -0.26 to 0.47; p = 0.540), with 19.4% of cases showing a shift from high HER2 expression in primary tumors to low expression in metastatic LNs. Patients treated with disitamab vedotin had an 80% objective response rate (ORR) and a 100% disease control rate (DCR), with no adverse events above grade 3-4. CONCLUSION: HER2 was frequently expressed in both primary tumors and metastatic LNs in EMPD patients, though heterogeneity was observed. HER2 status should be assessed in both primary and metastatic sites. Disitamab vedotin shows promise for treating HER2-positive advanced EMPD, warranting further study.

Source: Cancer Medicine

DOI: 10.1002/cam4.71274