P16 Overexpression in High-Grade Neuroendocrine Carcinomas of the Head and Neck Unrelated to HPV-Infection
Llucia Alos, Sofia Hakim, Leonardo Rodriguez, Ana B Larque, Nuria Guimera, Wim Quint, Margarita Alberola, Maria-Teresa Fernandez-Figueras, Antonio Cardesa, Jaume Ordi. Hospital Clinic, University of Barcelona, Barcelona, Spain; DDL Diagnostic Laboratory, Rijswijk, Netherlands; Hospital Valle Hebron, Barcelona, Spain; Hospital Universitari Germans Trias i Pujol, Badalona, Spain
Background: High-grade neuroendocrine carcinomas (HGNEC) of the head and neck are infrequent, aggressive neoplasms. Histologically they have the appearance of undifferentiated carcinomas and may have a striking similarity to HPV-associated squamous cell carcinomas of the head and neck, which usually are non-keratinizing carcinomas. P16 is considered a surrogate marker of HPV- associated squamous cell carcinomas of the head and neck. To our knowledge, this is the first report of a series of HGNEC of the head and neck in which a wide immunohistochemical panel including p16 has been performed and HPV has been investigated.
Design: Twelve HGNEC of the head and neck (5 parotid, 3 laryngeal, 2 sinonasal, 1 hypopharyngeal and 1 oral) were reviewed and a panel of immunohistochemical stains was performed: p16INK4a (mtm, Heildelberg, Germany - Roche Diagnostics), cytokeratin7 (clone OV-TL 12/30, Dako, Glostrup, Denmark), cytokeratin20 (clone Ks20.8, Dako), synaptophysin (clone SY38, Dako), chromogranin A (clone DAK-A3, Dako), CD56 (clone 123C3, Dako), neurofilament (clone 2F11, Dako), neuron-specific enolase (clone BBS/NC/Vi-H14, Dako), TTF-1 (clone 8G7G3/1, Dako), p53 (clone DO7, Dako), p63 (clone BC4A4, Biocare Medical, Egham, United Kingdom), and Ki67 (clone MIB-1, Dako). HPV analysis was performed by in situ hybridization (GenPoint HPV DNA Cocktail, Biotinylated, Dako) and by PCR, using the SPF10-DEIA-LiPA25 (Labo Bio-Medical Products, Rijswijk, Netherlands). RNaseP/PhHV qPCR was used to evaluate DNA quality and PCR inhibition.
Results: Eight tumors were small cell and four were large cell HGNEC. P16 was strong and diffusely positive in 100% of the neoplastic cells in 9/12 cases and had patchy positivity in 3/12 cases. The positivity of the remaining markers was as follows: cytokeratin7 5/12, cytokeratin20 6/12, synaptophysin 10/12, chromogranin A 9/12, CD56 11/12, neurofilament 11/12, neuron-specific enolase 10/12, TTF1 1/12, p53 11/12, and p63 2/12. All tumors had a proliferative index (Ki67) over 40%. HPV in situ hybridization and PCR were negative in all cases.
Conclusions: HGNEC of the head and neck frequently show a strong, diffuse positivity for p16, but they are not associated with HPV-infection. This must be considered in order to avoid the potential diagnostic pitfall with HPV-associated squamous cell carcinoma, a neoplasm with a better prognosis.
Category: Head & Neck
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 207, Wednesday Morning