Abstract：
Salivary duct carcinoma (SDC) is aggressive with limited therapeutic options. A subset of SDC display human epidermal growth factor receptor 2 (HER2) protein overexpression by immunohistochemistry, and some show ERBB2 gene amplification. Guidelines for HER2 scoring are not firmly established. Recent advances in breast carcinoma have established a role for anti-HER2 therapies in lesions with low HER2 expression lacking ERBB2 amplification. Delineating HER2 staining patterns in SDC is critical for evaluating anti-HER2 treatments. In total, 53 cases of SDC resected at our institution between 2004 and 2020 were identified. Androgen receptor (AR) and HER2 immunohistochemistry and ERBB2 fluorescence in situ hybridization were performed in all cases. AR expression was scored for percentage positive cells and categorized as positive (>10% of cells), low positive (1%-10%), or negative (<1%). HER2 staining levels and patterns were recorded, scored using 2018 ASCO/CAP guidelines, and categorized into HER2-positive (3+ or 2+ with ERBB2 amplification), HER2-low (1+ or 2+ without ERBB2 amplification), HER2-very low (faint staining in <10% of cells), or HER2-absent types. Clinical parameters and vital status were recorded. Median age was 70 years, with a male predominance. ERBB2-amplified tumors (11/53; 20.8%) presented at lower pT stages (pTis/pT1/pT2; P = .005, Fisher exact test) and more frequently had perineural invasion (P = .007, Fisher exact test) compared with ERBB2 nonamplified tumors; no other pathologic features differed significantly by gene amplification status. In addition, 2+ HER2 staining by 2018 ASCO/CAP criteria was most common (26/53; 49%); only 4 cases (8%) were HER2-absent status; 3+ HER2 staining was found in 9 tumors, and all were ERBB2 amplified. Six patients with HER2-expressing tumors received trastuzumab therapy, including 2 with ERBB2-amplified tumors. Overall survival and recurrence-free survival did not differ significantly based on ERBB2 status. This work suggests that 2018 ASCO/CAP guidelines for HER2 evaluation in breast carcinoma could be applied to SDC. Our findings also show broad overexpression of HER2 in SDC raising the possibility that more patients may benefit from anti-HER2-directed therapies.
摘要：
唾液导管癌（SDC）具有侵袭性，治疗选择有限。SDC的一个子集通过免疫组织化学显示人类表皮生长因子受体2（HER2）蛋白过表达，和一些显示ERBB2基因扩增。HER2评分指南尚未确立。乳腺癌的最新进展已经确立了抗HER2治疗在缺乏ERBB2扩增的低HER2表达的病变中的作用。在SDC中描绘HER2染色模式对于评估抗HER2治疗至关重要。确定了2004年至2020年间在我们机构切除的53例SDC病例。所有病例均进行雄激素受体（AR）和HER2免疫组织化学和ERBB2FISH。对AR表达的阳性细胞百分比进行评分，并归类为阳性（>10％的细胞），低阳性（1-10%），或阴性(<1%)。记录HER2染色水平和模式，使用2018年ASCO/CAP指南进行评分，并分为HER2阳性（3+或2+与ERBB2扩增），HER2低（1+或2+无ERBB2扩增），HER2-非常低（<10％的细胞中有微弱的染色），或HER2缺失。记录临床参数和生命状态。中位年龄为70岁，男性占优势。与ERBB2非扩增肿瘤相比，ERBB2扩增肿瘤（11/53;20.8％）在较低的pT阶段（pTis/pT1/pT2，p=0.005，Fisher精确检验）出现，并且更频繁地出现神经周浸润（p=0.007，Fisher精确检验）。基因扩增状态没有其他病理特征显着差异。根据2018年ASCO/CAP标准，2+HER2染色最常见(26/53;49%);只有4例(8%)没有HER2。在9个肿瘤中发现3+HER2染色,并且全部为ERBB2扩增。6例HER2表达肿瘤患者接受曲妥珠单抗治疗，包括2个ERBB2扩增的肿瘤。根据ERBB2状态，总生存率和无复发生存率没有显着差异。这项工作表明，2018年ASCO/CAP乳腺癌HER2评估指南可应用于SDC。我们的发现还表明，HER2在SDC中的广泛过度表达增加了更多患者可能从抗HER2定向治疗中受益的可能性。
