p16 overexpression in high-grade neuroendocrine carcinomas of the head and neck: potential diagnostic pitfall with HPV-related carcinomas
p16 overexpression in high-grade neuroendocrine carcinomas of the head and neck: potential diagnostic pitfall with HPV-related carcinomas
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DOI：
10.1007/s00428-016-1982-1
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发表时间：
2016-09-01
期刊：
影响因子：
3.5
通讯作者：
Ordi, Jaume
中科院分区：
文献类型：
--
作者：
Alos, Llucia;Hakim, Sofia;Ordi, Jaume
头颈部高级神经内分泌癌（hgnec）具有未分化癌的形态学表现，在组织学上可能与头颈部人类乳头状瘤病毒（HPV）相关的非角化鳞状细胞癌相似。本研究的目的是在组织学、免疫组织化学和病毒学上描述这些不寻常的肿瘤。19例头颈部hgnec（1例口咽部，5例鼻窦，7例喉部，6例腮腺）通过免疫组化小组进行了回顾和分析，特别强调细胞周期蛋白。采用原位杂交（GenPoint HPV, Dako）和PCR （SPF10-DEIA-LiPA(25)）检测肿瘤的HPV。用CM2B4抗体对默克尔细胞多瘤病毒进行了研究。小细胞型15例，大细胞型4例。大多数肿瘤（14/19,73.7%），包括所有纯小细胞癌，p16呈强弥漫性阳性染色。其中11例（78.5%）Rb缺失，cyclin D1表达低或缺失。所有病例HPV和多瘤病毒检测均为阴性。大多数患者是吸烟者，在疾病的晚期被诊断出来，结果很差，5年生存率为18%。总之，头颈部的hgnec与HPV感染很少相关，但由于Rb通路失调，通常表现出强烈的弥漫性p16阳性免疫染色。了解这种免疫组织化学表达模式可以避免hpv相关的非角化鳞状细胞癌的潜在诊断缺陷，后者预后较好。
High-grade neuroendocrine carcinomas (HGNECs) of the head and neck have the morphological appearance of undifferentiated carcinomas and could be histologically similar to human papillomavirus (HPV)-associated non-keratinizing squamous cell carcinomas of the head and neck. The aim of the study is to characterize histologically, immunohistochemically, and virologically these unusual neoplasms. Nineteen HGNECs of the head and neck (1 oropharyngeal, 5 sinonasal, 7 of the larynx, and 6 of the parotid gland) were reviewed and analyzed with a immunohistochemical panel, with special emphasis on cell cycle proteins. The tumors were tested for HPV by in situ hybridization (GenPoint HPV, Dako) and PCR (SPF10-DEIA-LiPA(25)). Merkel cell polyomavirus was studied using the antibody CM2B4. Fifteen HGNEC were of small cell and 4 of large cell type. Most of the tumors (14/19, 73.7 %), including all the pure small cell carcinomas, showed a strong and diffuse positive staining for p16. Eleven of them (78.5 %) had Rb loss and a low or absent cyclin D1 expression. All cases were negative for HPV and polyomavirus. Most patients were smokers, diagnosed at advanced stages of the disease, and had a poor outcome, with a 5-year survival of 18 %. In conclusion, HGNECs of the head and neck are infrequently related to HPV infection, but usually show strong, diffuse positive p16 immunostaining due to Rb pathway dysregulation. Awareness of this immunohistochemical pattern of expression may avoid a potential diagnostic pitfall with HPV-associated non-keratinizing squamous cell carcinomas, which have a better prognosis.