Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne Medical Centre, Cologne, Germany.
Head Neck. 2013 Nov;35(11):1521-6. doi: 10.1002/hed.23190. Epub 2013 Jan 23.
Carcinoma of unknown primary (CUP) of the neck are heterogeneous tumors in their clinical and biological characteristics, and a preoperative prognostic marker is desirable to optimize staging and therapy and to improve outcome and survival. For CUP syndrome, no optimized diagnostic and treatment strategy or biomarker have yet been determined.
Forty-seven patients presenting with CUP syndrome were analyzed after thorough standard diagnostic staging procedures. All patients were surgically treated with tonsillectomy, neck dissection of the diseased neck, as well as adjuvant chemoradiation. The tissue of lymph node metastases (and, if found, of the primary tumor) was analyzed regarding expression of p16, epidermal growth factor receptor (EGFR), and presence of human papillomavirus (HPV) DNA.
In 39% of all cases (20 of 47), the primary cancer was found during diagnostic workup. If HPV DNA was detected in the neck lymph node metastasis, the primary cancer was significantly more frequently found in the oropharynx (p = .002). Patients with a p16-positive tumor had a significantly higher 5-year overall survival (OS; 33% vs 69%; p = .045, disease-free survival [DSF] 77% vs 89%; p = not significant [NS]). Patients with p16-positive neck metastasis and no detectable primary cancer had a better prognosis. Expression of EGFR in this series did not have a significant effect on prognosis.
In patients presenting with CUP syndrome, p16 immunohistochemistry can serve to locate the primary cancer in the oropharynx. It is a positive prognostic indicator in patients with those heterogeneous cancers.
颈部不明原发癌（CUP）在临床和生物学特征上具有异质性，因此需要一种术前预后标志物来优化分期和治疗，并改善预后和生存。对于 CUP 综合征，尚未确定优化的诊断和治疗策略或生物标志物。
对 47 例经彻底标准诊断分期程序诊断为 CUP 综合征的患者进行分析。所有患者均接受扁桃体切除术、患侧颈部淋巴结清扫术以及辅助放化疗治疗。分析颈部淋巴结转移组织（如有原发性肿瘤）中 p16、表皮生长因子受体（EGFR）的表达情况以及人乳头瘤病毒（HPV）DNA 的存在情况。
在所有病例中（47 例中有 19 例），39%（20/47）的患者在诊断性检查中发现了原发性肿瘤。如果在颈部淋巴结转移灶中检测到 HPV DNA，则原发性肿瘤更常发生在口咽（p=0.002）。p16 阳性肿瘤患者的 5 年总生存率（OS；33% vs. 69%；p=0.045，无病生存率[DFS]77% vs. 89%；p=不显著[NS]）显著更高。p16 阳性颈部转移且未检测到原发性肿瘤的患者预后更好。在本系列中，EGFR 的表达对预后没有显著影响。
在出现 CUP 综合征的患者中，p16 免疫组化可用于定位口咽部的原发性肿瘤。在这些异质性癌症患者中，它是一个阳性预后指标。
