Squamous and Neuroendocrine Specific Immunohistochemical Markers in Head and Neck Squamous Cell Carcinoma: A Tissue Microarray Study
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The performance characteristics of neuroendocrine-specific and squamous-specific immunohistochemical markers in head and neck squamous cell carcinomas (SCC), in particular in oropharyngeal tumors in this era of human papillomavirus (HPV)-induced cases, are not well-established. The differential diagnosis for poorly differentiated SCCs, for nonkeratinizing oropharyngeal SCCs, and for other specific SCC variants such as basaloid SCC and undifferentiated (or lymphoepithelial-like) carcinomas includes neuroendocrine carcinomas. Given that neuroendocrine carcinomas of the head and neck are aggressive regardless of HPV status, separating them from SCC is critically important. In this study, we examined the neuroendocrine markers CD56, synaptophysin, and chromogranin-A along with the squamous markers p40 and cytokeratin 5/6 in a large tissue microarray cohort of oral, oropharyngeal, laryngeal, and hypopharyngeal SCCs with known HPV results by RNA in situ hybridization for the oropharyngeal tumors. Results were stratified by site and specific SCC variant. The neuroendocrine stains were rarely expressed in SCC (<1% overall) with CD56 the least, and chromogranin-A the most, specific markers. Further, p40 and cytokeratin 5/6 were very consistently expressed in all head and neck SCC (>98% overall), including very strong, consistent staining in oropharyngeal HPV-related nonkeratinizing SCC. Undifferentiated (or lymphoepithelial-like) carcinomas of the oropharynx are more frequently p40 or cytokeratin 5/6 negative or show only weak or focal expression. In summary, markers of neuroendocrine and squamous differentiation show very high specificity and sensitivity, respectively, across the different types of head and neck SCC.
KeywordsOropharyngeal Squamous cell carcinoma p40 Neuroendocrine Immunohistochemistry Head and neck Human papillomavirus
We would like to thank Donna M. Posey for her wonderful assistance with clerical support and spreadsheet data management for the various aspects of this study. We also acknowledge the Translational Pathology Shared Resource (TPSR) supported by NCI/NIH Cancer Center Support Grant 2P30 CA068485-14 and the Vanderbilt Mouse Metabolic Phenotyping Center Grant 5U24DK059637-13.
- 18.Cardesa A, Zidar N, Alos L. Adenosquamous carcinoma. In: Barnes L, Eveson J, Reichart P, Sidransky D, editors. Pathology and genetics head and neck tumours. Lyon: IARC Press; 2005. p. 130–1.Google Scholar
- 19.Cardesa A, Zidar N, Ereno C. Basaloid squamous cell carcinoma. In: Barnes EL, Eveson JW, Reichart P, Sidranksy D, editors. World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Lyon: IARC Press; 2005. p. 125–6.Google Scholar
- 22.Lewis JS Jr, Ukpo OC, Ma XJ, Flanagan JJ, Luo Y, Thorstad WL, et al. Transcriptionally-active high-risk human papillomavirus is rare in oral cavity and laryngeal/hypopharyngeal squamous cell carcinomas: a tissue microarray study utilizing E6/E7 mRNA in situ hybridization. Histopathology. 2012;60(6):982–91.CrossRefPubMedGoogle Scholar
- 23.Ukpo OC, Flanagan JJ, Ma XJ, Luo Y, Thorstad WL, Lewis JS Jr. High-risk human papillomavirus E6/E7 mRNA detection by a novel in situ hybridization assay strongly correlates with p16 expression and patient outcomes in oropharyngeal squamous cell carcinoma. Am J Surg Pathol. 2011;35(9):1343–50.CrossRefPubMedGoogle Scholar
- 24.Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6(2):244–85.CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Bishop JA, Montgomery EA, Westra WH. Use of p40 and p63 immunohistochemistry and human papillomavirus testing as ancillary tools for the recognition of head and neck sarcomatoid carcinoma and its distinction from benign and malignant mesenchymal processes. Am J Surg Pathol. 2014;38(2):257–64.CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Westra W, Boy S, El-Mofty SK, Gillison M, Schwartz MR, Syrjanen S, et al. Squamous cell carcinoma, HPV-positive. In: El-Naggar A, Chan JKC, Grandis JR, Takata T, Slootweg PJ, editors. WHO classification of head and neck tumours. 4th ed. Lyon: IARC Press; 2017. p. 136–8.Google Scholar