Background: Human papillomavirus (HPV)-related multi phenotypic sinonasal carcinoma (HMSC) is a recently described tumor subtype with an unknown prognosis, often misdiagnosed with other sinonasal carcinomas, and associated with high-risk HPV (HR-HPV). The present study aimed to evaluate the expression of vascular endothelial growth factor (VEGF), Bcl-2-associated X protein (BAX), epidermal growth factor receptors (EGFR), ProEx™C, and human telomerase reverse transcriptase (hTERT) and assess their association with survival and clinicopathological characteristics. Methods: Between 2017 and 2022, 40 HMSC patients underwent surgical resection at the School of Medicine, Zagazig University Hospitals (Zagazig, Egypt). Tissue samples were examined for the presence of HR-HPV; absence of myeloblastosis (MYB), MYB proto-oncogene like 1 (MYBL1), and nuclear factor I/B (NFIB) fusions and the presence of myoepithelial proteins (calponin, S100, SMA), squamous differentiation markers (p63, p40, calponin), VEGF, BAX, ProEx™C, and hTERT by immunohistochemistry. All patients were followed up for about 54 months until death or the last known survival data. Data were analyzed using the Chi square test and Kaplan-Meier method. Results: The expression of VEGF, hTERT, and ProEx™C was significantly associated with age, advanced tumor stages, lymph node metastasis, tumor size, mortality, relapse, poor disease-free survival (DFS), and overall survival (OS) (P<0.001). BAX expression was significantly associated with tumor size, age, poor DFS, and relapse (P=0.01, P<0.001, P=0.035, and P=0.002, respectively). Conclusion: HMSC is strongly associated with HR-HPV. The expression of VEGF, EGFR, BAX, hTERT, and ProEx™C is associated with aggressive malignant behavior, poor survival, and poor prognosis, making them novel prognostic biomarkers for targeted therapeutics in HMSC. |
- XI IC. Cancer Incidence in Five Continents Volume XI. Lyon: IARC; 2019.
- Boceila E, Atef A, Hassan M, Ali M, Khalele B, Shaban M. Epidemiology of orofacial malignancies in Egypt (2016-2021): A reappraisal account. Advances in Clinical and Experimental Dentistry. 2022;2:24-36. doi: 10.21608/aced.2021.247509.
- Demers PA, Kogevinas M, Boffetta P, Leclerc A, Luce D, Gerin M, et al. Wood dust and sino-nasal cancer: pooled reanalysis of twelve case-control studies. Am J Ind Med. 1995;28:151-66. doi: 10.1002/ajim.4700280202. PubMed PMID: 8585514.
- Slack R, Young C, Rushton L, British Occupational Cancer Burden Study G. Occupational cancer in Britain. Nasopharynx and sinonasal cancers. Br J Cancer. 2012;107:S49-55. doi: 10.1038/bjc.2012.118. PubMed PMID: 22710679; PubMed Central PMCID: PMCPMC3384014.
- Ahn B, Kim E, Oh H, Chae YS, Kim CH, Lee Y, et al. Human Papillomavirus-Related Multiphenotypic Sinonasal Carcinoma with Late Recurrence. J Pathol Transl Med. 2019;53:337-40. doi: 10.4132/jptm.2019.04.02. PubMed PMID: 31022777; PubMed Central PMCID: PMCPMC6755653.
- Bishop JA, Guo TW, Smith DF, Wang H, Ogawa T, Pai SI, et al. Human papillomavirus-related carcinomas of the sinonasal tract. Am J Surg Pathol. 2013;37:185-92. doi: 10.1097/PAS.0b013e3182698673. PubMed PMID: 23095507; PubMed Central PMCID: PMCPMC3545097.
- Chen J. Signaling pathways in HPV-associated cancers and therapeutic implications. Rev Med Virol. 2015;25:24-53. doi: 10.1002/rmv.1823. PubMed PMID: 25752815.
- Lydiatt WM, Patel SG, O’Sullivan B, Brandwein MS, Ridge JA, Migliacci JC, et al. Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67:122-37. doi: 10.3322/caac.21389. PubMed PMID: 28128848.
- Key M. Immunohistochemistry staining methods. Education Guide Immunohistochemical Staining Methods Fourth Edition. 2006:47.
- Bishop JA, Andreasen S, Hang JF, Bullock MJ, Chen TY, Franchi A, et al. HPV-related Multiphenotypic Sinonasal Carcinoma: An Expanded Series of 49 Cases of the Tumor Formerly Known as HPV-related Carcinoma With Adenoid Cystic Carcinoma-like Features. Am J Surg Pathol. 2017;41:1690-701. doi: 10.1097/PAS.0000000000000944. PubMed PMID: 28877065; PubMed Central PMCID: PMCPMC5680105.
- Hagmar B, Johansson B, Kalantari M, Petersson Z, Skyldberg B, Walaas L. The incidence of HPV in a Swedish series of invasive cervical carcinoma. Med Oncol Tumor Pharmacother. 1992;9:113-7. doi: 10.1007/BF02987743. PubMed PMID: 1341323.
- Bishop JA, Ogawa T, Stelow EB, Moskaluk CA, Koch WM, Pai SI, et al. Human papillomavirus-related carcinoma with adenoid cystic-like features: a peculiar variant of head and neck cancer restricted to the sinonasal tract. Am J Surg Pathol. 2013;37:836-44. doi: 10.1097/PAS.0b013e31827b1cd6. PubMed PMID: 23598962; PubMed Central PMCID: PMCPMC3653997.
- Ramos-Vara JA. Technical aspects of immunohistochemistry. Vet Pathol. 2005;42:405-26. doi: 10.1354/vp.42-4-405. PubMed PMID: 16006601.
- Alabiad MA, Elderey MS, Shalaby AM, Nosery Y, Gobran MA. The Usefulness of 4 Immunoperoxidase Stains Applied to Urinary Cytology Samples in the Pathologic Stage of Urothelial Carcinoma: A Study With Histologic Correlation. Appl Immunohistochem Mol Morphol. 2021;29:422-32. doi: 10.1097/PAI.0000000000000905. PubMed PMID: 33480604.
- Khayal EE, Alabiad MA, Elkholy MR, Shalaby AM, Nosery Y, El-Sheikh AA. The immune modulatory role of marjoram extract on imidacloprid induced toxic effects in thymus and spleen of adult rats. Toxicology. 2022;471:153174. doi: 10.1016/j.tox.2022.153174. PubMed PMID: 35398170.
- Tawfeek SE, Shalaby AM, Alabiad MA, Albackoosh AAA, Albakoush KMM, Omira MMA. Metanil yellow promotes oxidative stress, astrogliosis, and apoptosis in the cerebellar cortex of adult male rat with possible protective effect of scutellarin: A histological and immunohistochemical study. Tissue Cell. 2021;73:101624. doi: 10.1016/j.tice.2021.101624. PubMed PMID: 34419739.
- Alabiad MA, Harb OA, Hefzi N, Ahmed RZ, Osman G, Shalaby AM, et al. Prognostic and clinicopathological significance of TMEFF2, SMOC-2, and SOX17 expression in endometrial carcinoma. Exp Mol Pathol. 2021;122:104670. doi: 10.1016/j.yexmp.2021.104670. PubMed PMID: 34339705.
- Shalaby AM, Aboregela AM, Alabiad MA, El Shaer DF. Tramadol Promotes Oxidative Stress, Fibrosis, Apoptosis, Ultrastructural and Biochemical alterations in the Adrenal Cortex of Adult Male Rat with Possible Reversibility after Withdrawal. Microsc Microanal. 2020;26:509-23. doi: 10.1017/S1431927620001397. PubMed PMID: 32366353.
- Shamloo N, Taghavi N, Yazdani F, Azimian P, Ahmadi S. Evaluation of VEGF expression correlates with COX-2 expression in pleomorphic adenoma, mucoepidermoid carcinoma and adenoid cystic carcinoma. Dent Res J (Isfahan). 2020;17:100-6. doi: 10.4103/1735-3327.280887. PubMed PMID: 32435431; PubMed Central PMCID: PMCPMC7224257.
- Rupp NJ, Camenisch U, Seidl K, Rushing EJ, Anderegg N, Broglie MA, et al. HPV-Related Multiphenotypic Sinonasal Carcinoma: Four Cases that Expand the Morpho-Molecular Spectrum and Include Occupational Data. Head Neck Pathol. 2020;14:623-9. doi: 10.1007/s12105-019-01079-1. PubMed PMID: 31571045; PubMed Central PMCID: PMCPMC7413931.
- Hang JF, Hsieh MS, Li WY, Chen JY, Lin SY, Liu SH, et al. Human papillomavirus-related carcinoma with adenoid cystic-like features: a series of five cases expanding the pathological spectrum. Histopathology. 2017;71:887-96. doi: 10.1111/his.13301. PubMed PMID: 28664668.
- Lee SK, Kwon MS, Lee YS, Choi SH, Kim SY, Cho KJ, et al. Prognostic value of expression of molecular markers in adenoid cystic cancer of the salivary glands compared with lymph node metastasis: a retrospective study. World J Surg Oncol. 2012;10:266. doi: 10.1186/1477-7819-10-266. PubMed PMID: 23231994; PubMed Central PMCID: PMCPMC3556129.
- Ward ML, Kernig M, Willson TJ. HPV-Related Multiphenotypic Sinonasal Carcinoma: A Case Report and Literature Review. Laryngoscope. 2021;131:106-10. doi: 10.1002/lary.28598. PubMed PMID: 32159863.
- Ettl T, Schwarz S, Kleinsasser N, Hartmann A, Reichert TE, Driemel O. Overexpression of EGFR and absence of C-KIT expression correlate with poor prognosis in salivary gland carcinomas. Histopathology. 2008;53:567-77. doi: 10.1111/j.1365-2559.2008.03159.x. PubMed PMID: 18983466.
- Park S, Nam SJ, Keam B, Kim TM, Jeon YK, Lee SH, et al. VEGF and Ki-67 Overexpression in Predicting Poor Overall Survival in Adenoid Cystic Carcinoma. Cancer Res Treat. 2016;48:518-26. doi: 10.4143/crt.2015.093. PubMed PMID: 26194375; PubMed Central PMCID: PMCPMC4843710.
- Xie X, Nordgard S, Clausen OPF, Boysen M. Prognostic significance of Bax and Bcl-2 expressions in adenoid cystic carcinoma of major and minor salivary glands of nasal and oral epithelium. The Open Otorhinolaryngology Journal. 2010;4.
- Goulart-Filho JAV, Montalli VAM, Passador-Santos F, de Araujo NS, de Araujo VC. Role of apoptotic, autophagic and senescence pathways in minor salivary gland adenoid cystic carcinoma. Diagn Pathol. 2019;14:14. doi: 10.1186/s13000-019-0796-2. PubMed PMID: 30736793; PubMed Central PMCID: PMCPMC6368765.
- Kungoane T. The prognostic significance of proliferation markers Ki-67 and MCM2 and p53 protein expression in salivary gland neoplasms. Johannesburg: University of the Witwatersrand; 2015.
- Ghazy SE, Helmy IM, Baghdadi HM. Maspin and MCM2 immunoprofiling in salivary gland carcinomas. Diagn Pathol. 2011;6:89. doi: 10.1186/1746-1596-6-89. PubMed PMID: 21943228; PubMed Central PMCID: PMCPMC3191357.
- Vivatvakin S, Ratchataswan T, Leesutipornchai T, Ruangritchankul K, Keelawat S, Mahattanasakul P, et al. MCM-2, Ki-67, and EGFR downregulated expression levels in advanced stage laryngeal squamous cell carcinoma. Sci Rep. 2021;11:14607. doi: 10.1038/s41598-021-94077-9. PubMed PMID: 34272446; PubMed Central PMCID: PMCPMC8285532.
- Shigeishi H, Sugiyama M, Tahara H, Ono S, Kumar Bhawal U, Okura M, et al. Increased telomerase activity and hTERT expression in human salivary gland carcinomas. Oncol Lett. 2011;2:845-50. doi: 10.3892/ol.2011.354. PubMed PMID: 22866138; PubMed Central PMCID: PMCPMC3408017.
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