Scherrer Emilie, Kang Ashley, Bloudek Lisa M, Koshkin Vadim S
Seagen, Inc., Bothell, WA, United States.
Curta, Inc., Seattle, WA, United States.
Front Oncol. 2022 Oct 21;12:1011885. doi: 10.3389/fonc.2022.1011885. eCollection 2022.
Urothelial carcinoma (UC) is a common malignancy with significant associated mortality. Recent clinical trials suggest an emerging role for HER2-targeted therapy. Testing for HER2 expression in UC is not part of current routine clinical practice. In consequence, the prevalence of HER2 expression in UC is not well defined.
A systematic literature review (SLR) was conducted to characterize HER2 expression in both locally advanced unresectable or metastatic (LA/mUC) and earlier stage UC, classified as HER2+, HER2-low, HER2-. HER2+ was defined as an immunohistochemistry (IHC) score of 3+ or IHC 2+ and ISH/FISH+. HER2-low was defined as an IHC score of 2+ and ISH/FISH- or IHC 1+. HER2- was defined as an IHC score of 0. Weighted averages were calculated to generate an estimate of the population prevalence.
A total of 88 studies were identified, with 45, 30, and 13 studies investigating LA/mUC, earlier stage UC, and mixed stage/unspecified, respectively. The most common assays used were Dako HercepTest and Ventana Pathway anti-HER2/neu (4B5) for IHC to assess HER2 protein expression; Abbott PathVysion HER-2 DNA Probe Kit, FoundationOne CDx, and Guardant360 CDx for assessing HER2 gene amplification. The most frequently cited scoring guidelines were ASCO/CAP guidelines for breast cancer and gastric cancer, though most studies defined their own criteria for HER2 expression. Using the pre-specified definition, HER2+ prevalence ranged from 6.7% to 37.5% with a weighted average of 13.0% in LA/mUC. Only 1 study presented data that could be classified as HER2+ based on pre-specified criteria in earlier stage UC patients, and this study represented a likely outlier, at 76.0%.
The results from this SLR help to shed light on HER2 expression in UC, a potentially clinically relevant biomarker-driven subpopulation for emerging HER2-directed regimens. Results of this SLR illuminate the variability in how HER2+ status expression levels are being assessed and how HER2+ is defined. Consensus on standardized HER2 testing and scoring criteria is paramount to better understand the clinical relevance in patients with UC.
尿路上皮癌（UC）是一种常见的恶性肿瘤，具有较高的相关死亡率。近期临床试验表明，HER2靶向治疗正发挥着越来越重要的作用。检测UC中的HER2表达并非当前常规临床实践的一部分。因此，UC中HER2表达的患病率尚不明确。
进行了一项系统文献综述（SLR），以描述局部晚期不可切除或转移性（LA/mUC）以及早期UC中HER2的表达情况，分为HER2阳性、HER2低表达、HER2阴性。HER2阳性定义为免疫组织化学（IHC）评分为3+或IHC 2+且原位杂交/荧光原位杂交（ISH/FISH）阳性。HER2低表达定义为IHC评分为2+且ISH/FISH阴性或IHC 1+。HER2阴性定义为IHC评分为0。计算加权平均值以估计总体患病率。
共纳入88项研究，其中45项、30项和13项研究分别调查LA/mUC、早期UC以及混合分期/未明确分期的情况。最常用的检测方法是用于评估HER2蛋白表达的免疫组化检测，即Dako HercepTest和Ventana Pathway抗HER2/neu（4B5）；用于评估HER2基因扩增的Abbott PathVysion HER-2 DNA探针试剂盒、FoundationOne CDx和Guardant360 CDx。最常引用的评分指南是美国临床肿瘤学会/美国病理学家协会（ASCO/CAP）关于乳腺癌和胃癌的指南，不过大多数研究都自行定义了HER2表达的标准。根据预先设定的定义，LA/mUC中HER2阳性患病率在6.7%至37.5%之间，加权平均值为13.0%。在早期UC患者中，只有1项研究提供了根据预先设定标准可归类为HER2阳性的数据，该研究的患病率为76.0%，可能是个异常值。
这项SLR的结果有助于阐明UC中HER2的表达情况，HER2是一种潜在的临床相关生物标志物驱动的亚群，适用于新兴的HER2导向治疗方案。这项SLR的结果揭示了HER2阳性状态表达水平评估方式以及HER2阳性定义的变异性。对标准化HER2检测和评分标准达成共识对于更好地理解UC患者的临床相关性至关重要。
