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Abstract：
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.
摘要：
肺部是头颈部（H＆N）鳞状细胞癌（SCC）转移的常见部位。这项研究试图定义p16免疫表达和HPV在肺原发性SCC中的存在，并确定它们在区分原发性肺SCC和与HPV相关的口咽原发性转移中的有用性。在病理档案中搜索患有肺SCC而其他地方没有SCC的患者。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。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HPVDNA阳性病例。25例(32%)中有8例显示p16的细胞质和核表达:2例(8%)强,2例(8%)中等,在>70%的肿瘤细胞中;1例(4%)强,1（4%）中度，和1(4%)在50-70%的肿瘤细胞中弱;1(4%)在<50%的肿瘤细胞中弱。所有病例ISHE6/E7mRNA均为阴性。8例p16表达病例中有7例（87.5％）可用于HPVPCR检测；所有HPVDNA均为阴性。还确定了12例可能具有SCC转移到肺的患者的回顾性对照组；3例存在高危HPVDNA，证实了转移。p16在肺SCC中的表达并不少见，并且可能无法区分原发性肺SCC和HPV相关口咽原发性转移。验证性HPV检测（高危HPVDNA或E6/E7mRNA）建议区分口咽原发转移和两个单独的原发转移。
