Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Mayo Clinic Alix School of Medicine, Rochester, MN, USA.
Head Neck Pathol. 2020 Dec;14(4):951-965. doi: 10.1007/s12105-020-01163-x. Epub 2020 Apr 29.
Salivary duct carcinoma (SDC) commonly expresses androgen receptor (AR) and HER2, giving rise to treatment implications. SDC may also express programmed-death-ligand-1 (PD-L1), a predictive marker of response to checkpoint inhibitors. PD-L1 can be associated with genomic instability and high density of tumor infiltrating lymphocytes (TILs). Evaluation of HER2 immunohistochemistry (IHC) in SDC is not standardized, and relationships between ERBB2 copy numbers, PD-L1 expression and TILs in SDC are unknown. We evaluated 32 SDCs for HER2, AR and PD-L1 expression (IHC), ERBB2 status (FISH) and TILs (slide review). HER2 was scored with three different systems (breast, gastric, proposed salivary gland). PD-L1 was evaluated with the combined positive score. Most patients were older men, presenting at advanced clinical stage with nodal or distant metastases. During follow-up (mean 5 years, range 6 months to 21 years), 25 of the 32 patients (78%) died of SDC. We propose a HER2 IHC scoring system which accurately predicts underlying ERBB2 amplification or increased copy numbers in SDC. Most tumors had increased ERBB2 copy numbers (19/32 amplification, 6/32 aneusomy), a finding associated with higher TIL densities (p = 0.045) and PD-L1 expression (p = 0.025). Patients with TILs ≥ 40% had better prognoses (Log-Rank p = 0.013), with TILs being favorable prognosticators in univariate analysis (Hazard ratio: 0.18, p = 0.024). A subset of SDCs with increased ERBB2 copy numbers have higher TILs and PD-L1 expression. TILs ≥ 40% are associated with better prognosis.
涎腺癌（SDC）通常表达雄激素受体（AR）和 HER2，这为治疗带来了影响。SDC 也可能表达程序性死亡配体-1（PD-L1），这是对检查点抑制剂反应的预测标志物。PD-L1 可与基因组不稳定性和肿瘤浸润淋巴细胞（TIL）密度高相关。SDC 中 HER2 免疫组化（IHC）的评估尚未标准化，并且 ERBB2 拷贝数、SDC 中 PD-L1 表达和 TIL 之间的关系尚不清楚。我们评估了 32 例 SDC 中 HER2、AR 和 PD-L1 表达（IHC）、ERBB2 状态（FISH）和 TILs（幻灯片评估）。HER2 采用三种不同的系统（乳腺、胃、拟议的唾液腺）进行评分。PD-L1 采用联合阳性评分进行评估。大多数患者为老年男性，临床分期较晚，存在淋巴结或远处转移。在随访期间（平均 5 年，范围 6 个月至 21 年），32 例患者中的 25 例（78%）死于 SDC。我们提出了一种 HER2 IHC 评分系统，该系统可准确预测 SDC 中潜在的 ERBB2 扩增或拷贝数增加。大多数肿瘤具有增加的 ERBB2 拷贝数（19/32 扩增，6/32 非整倍体），这与更高的 TIL 密度相关（p=0.045）和 PD-L1 表达（p=0.025）。TILs≥40%的患者具有更好的预后（对数秩检验 p=0.013），在单因素分析中 TILs 是有利的预后因素（风险比：0.18，p=0.024）。具有增加的 ERBB2 拷贝数的 SDC 亚组具有更高的 TILs 和 PD-L1 表达。TILs≥40%与更好的预后相关。
