Department of Pathology, The University of Chicago, 5841 S. Maryland Ave , Chicago, IL, 60637, USA.
OSF Little Company of Mary Medical Center, Evergreen Park, IL, USA.
Head Neck Pathol. 2020 Dec;14(4):966-973. doi: 10.1007/s12105-020-01165-9. Epub 2020 Apr 29.
The lungs are a common site of metastasis of head and neck (H&N) squamous cell carcinomas (SCC). This study attempts to define p16 immunoexpression and presence of HPV in primary SCC of the lung and determine their usefulness in discriminating between primary lung SCC and metastasis from HPV-associated oropharyngeal primary. Pathology archives were searched for patients with SCC of the lung without SCC elsewhere. Tissue microarray was constructed and immunohistochemistry performed using anti-p40 and anti-p16 antibodies. All cases were tested for HPV viral proteins E6/E7 by RNA in situ hybridization (ISH) and available positive cases for HPV DNA by polymerase chain reaction (PCR). Eight of 25 (32%) showed cytoplasmic and nuclear expression of p16: 2 (8%) strong and 2 (8%) moderate in > 70% of tumor cells; 1 (4%) strong, 1 (4%) moderate, and 1 (4%) weak in 50-70% of tumor cells; 1 (4%) weak in < 50% of tumor cells. E6/E7 mRNA ISH was negative in all cases. Seven of 8 (87.5%) p16-expressing cases were available for testing by HPV PCR; all were negative for HPV DNA. A retrospective control group of 12 patients with possible SCC metastatic to lung was also identified; high-risk HPV DNA was present in 3, confirming metastasis. p16 expression in lung SCC is not uncommon and may not discriminate between primary pulmonary SCC and metastasis from HPV-associated oropharyngeal primary. Confirmatory HPV testing (high risk HPV DNA or E6/E7 mRNA) is recommended to differentiate metastasis from oropharyngeal primary from two separate primaries.
肺部是头颈部（H&N）鳞状细胞癌（SCC）转移的常见部位。本研究试图定义原发性肺 SCC 中 p16 的免疫表达和 HPV 存在，并确定其在区分原发性肺 SCC 和 HPV 相关口咽原发性转移中的作用。搜索了无其他部位 SCC 的肺 SCC 患者的病理档案。构建组织微阵列，并使用抗 p40 和抗 p16 抗体进行免疫组织化学染色。所有病例均通过 RNA 原位杂交（ISH）检测 HPV 病毒蛋白 E6/E7，并通过聚合酶链反应（PCR）检测 HPV DNA。25 例中 8 例（32%）显示 p16 的细胞质和核表达：2 例（8%）强阳性和 2 例（8%）中度阳性，肿瘤细胞中>70%；1 例（4%）强阳性，1 例（4%）中度阳性，1 例（4%）弱阳性，肿瘤细胞中 50-70%；1 例（4%）弱阳性，肿瘤细胞中<50%。所有病例 E6/E7 mRNA ISH 均为阴性。8 例 p16 表达病例中 7 例（87.5%）可进行 HPV PCR 检测；所有病例均未检测到 HPV DNA。还确定了一组 12 例可能转移至肺部的 SCC 患者作为回顾性对照组；3 例存在高危 HPV DNA，证实为转移。肺 SCC 中 p16 的表达并不少见，不能区分原发性肺 SCC 和 HPV 相关口咽原发性转移。建议进行 HPV 确认检测（高危 HPV DNA 或 E6/E7 mRNA），以区分口咽原发性转移和两个独立原发性。
