Lu Xiaolin, Zhang Peipei, Zhu Yao, Ye Dingwei
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
Oncol Lett. 2019 Mar;17(3):2677-2686. doi: 10.3892/ol.2019.9930. Epub 2019 Jan 14.
The role of human epidermal growth factor receptor 2 (HER2) amplification as a biomarker for treatment in patients with lymph node (LN)-metastatic penoscrotal extramammary Paget's disease (EMPD) was investigated in the present study. A total of 11 male patients with LN-metastatic penoscrotal EMPD were retrospectively reviewed. Positron emission tomography/computed tomography (PET/CT) was conducted prior to surgery. Immunohistochemistry and fluorescence hybridization were used to evaluate HER2 gene amplification in LN samples. Sanger sequencing was used to investigate HER2 mutations. A literature review of the prevalence of HER2 amplification in EMPD and the efficacy of HER2-targeted therapy was also undertaken. PET/CT is effective in detecting metastatic sites. The sensitivity and specificity of PET/CT was 90.9 and 100.0% for inguinal LNs, and 85.7 and 80.0% for pelvic LNs, respectively. The median time from LN dissection to disease progression was 15.9±1.5 months. Of the 11 patients, 3 (27.3%) indicated HER2 amplification. Patients with HER2 amplification showed shorter median times from disease discovery to LN metastasis (HER2 amplification vs HER2 non-amplification; 15.6 vs. 10.0 months; P=0.50) and from LN dissection to disease progression (HER2 amplification vs. HER2 non-amplification, 16.2 vs. 13.6 months; P=0.11). However, the aforementioned observations were not indicated to be statistically significant. No HER2 mutations were identified. Trastuzumab, a HER2-targeted monoclonal antibody, was administered to 2 of the patients with HER2 amplification. A literature review of the prevalence of HER2 amplification in EMPD and the efficacy of HER2-targeted therapy showed similar results. Altogether, 485 cases of EMPD were reported, 35 of which had metastases. The results in the present study suggest that PET/CT should be used on all metastatic EMPD patients. EMPD may be effectively treated with trastuzumab. The present study and case reports from the literature provide evidence for the benefit of testing for HER2 amplification in this rare disease and highlight the requirement for a multicenter clinical trial to assess the impact of trastuzumab therapy in treating this disease.
本研究调查了人表皮生长因子受体2（HER2）扩增作为淋巴结（LN）转移的阴茎阴囊外Paget病（EMPD）患者治疗生物标志物的作用。回顾性分析了11例LN转移的阴茎阴囊EMPD男性患者。术前进行正电子发射断层扫描/计算机断层扫描（PET/CT）。采用免疫组织化学和荧光杂交技术评估LN样本中HER2基因扩增情况。采用Sanger测序法检测HER2突变。还对EMPD中HER2扩增的发生率及HER2靶向治疗的疗效进行了文献综述。PET/CT对检测转移部位有效。PET/CT对腹股沟LN的敏感性和特异性分别为90.9%和100.0%，对盆腔LN的敏感性和特异性分别为85.7%和80.0%。从LN清扫到疾病进展的中位时间为15.9±1.5个月。11例患者中，3例（27.3%）显示HER2扩增。HER2扩增患者从疾病发现到LN转移的中位时间（HER2扩增组与HER2未扩增组；15.6个月对10.0个月；P=0.50）以及从LN清扫到疾病进展的中位时间（HER2扩增组与HER2未扩增组，16.2个月对13.6个月；P=0.11）较短。然而，上述观察结果无统计学意义。未发现HER2突变。2例HER2扩增患者接受了HER2靶向单克隆抗体曲妥珠单抗治疗。对EMPD中HER2扩增的发生率及HER2靶向治疗的疗效进行的文献综述显示了类似结果。共报道485例EMPD病例，其中35例有转移。本研究结果表明，所有转移性EMPD患者均应使用PET/CT。曲妥珠单抗可有效治疗EMPD。本研究及文献中的病例报告为在这种罕见疾病中检测HER2扩增的益处提供了证据，并强调需要进行多中心临床试验以评估曲妥珠单抗治疗该病的效果。
