Abstract
Temporal bone squamous cell carcinoma (TBSCC) is an uncommon, aggressive malignancy with a poor prognosis in advanced cases. The dismal outcome is partially related to: the lack of reliable clinical or pathological prognostic factors and the largely unstandardized surgical and integrated treatments adopted. There is an undeniable need for novel diagnostic/therapeutic strategies to improve the prognosis. The purpose of this critical review was to explore the level of available knowledge concerning the molecular markers involved in the biology of TBSCC that have a prognostic potential. The Pub‐Med and Scopus electronic databases were searched without publication date limits for studies investigating molecular markers in cohorts of patients with primary TBSCC. The search terms used were: “temporal bone cancer”, “temporal bone carcinoma”, “temporal bone malignancy”, “ear cancer”, “ear carcinoma”, and “ear malignancy”. We decided preliminarily not to consider series with less than five cases. Nine retrospective case series of TBSCC were found in which different analytical techniques had been used to study the role of several biomarkers (HPV, vimentin, transforming growth factor β, CD105, RECK, matrix metalloproteinase-9, MASPIN, EBV, p16, TP53 mutation, pSTAT3, relaxin-2). CD105 expression (in tumor vessel endothelial cells) and MASPIN cytoplasmic expression (in carcinoma cells) were, respectively, found directly and inversely related with the neoplasm’s recurrence rate. CD105 expression was also inversely related with disease-free survival in TBSCC. A future goal of such analyses should be to ascertain the radio- and chemo-sensitivity profiles of individual TBSCCs, enabling truly personalized therapies. A further, more ambitious goal will be to find targets for therapeutic agents that might prove crucial in improving the disease-specific survival for patients with advanced TBSCC.
Similar content being viewed by others
References
Lionello M, Stritoni P, Facciolo MC et al (2014) Temporal bone carcinoma. Current diagnostic, therapeutic, and prognostic concepts. J Surg Oncol 110:383–392
Prasad SC, D’Orazio F, Medina M, Bacciu A, Sanna M (2014) State of the art in temporal bone malignancies. Curr Opin Otolaryngol Head Neck Surg 22:154–165
Takenaka Y, Cho H, Nakahara S, Yamamoto Y, Yasui T, Inohara H (2015) Chemoradiation therapy for squamous cell carcinoma of the external auditory canal: a meta-analysis. Head Neck 37:1073–1080
Zanoletti E, Marioni G, Franchella S et al (2015) Recurrent squamous cell carcinoma of the temporal bone: critical analysis of cases with a poor prognosis. Am J Otolaryngol 36:352–355
Marioni G, Blandamura S, Lionello M et al (2014) Indications for postoperative radiotherapy in laryngeal carcinoma: a panel of tumor tissue markers for predicting locoregional recurrence in surgically treated carcinoma. A pilot study. Head Neck 36:1534–1540
Strimbu K, Tavel JA (2010) What are biomarkers? Curr Opin HIV AIDS 5:463–466
Jin YT, Tsai ST, Li C et al (1997) Prevalence of human papillomavirus in middle ear carcinoma associated with chronic otitis media. Am J Pathol 150:1327–1333
Tsai ST, Li C, Jin YT, Chao WY, Su IJ (1997) High prevalence of human papillomavirus types 16 and 18 in middle-ear carcinomas. Int J Cancer 71:208–212
Masterson L, Winder DM, Marker A et al (2013) Investigating the role of human papillomavirus in squamous cell carcinoma of the temporal bone. Head Neck Oncology 5:22
Marioni G, Nucci R, Marino F et al (2012) Neoangiogenesis in temporal bone carcinoma: the prognostic role of CD105. Otol Neurotol 33:843–848
Marioni G, Zanoletti E, Stritoni P et al (2013) Expression of the tumour-suppressor maspin in temporal bone carcinoma. Histopathology 63:242–249
Marioni G, Nucci R, Marino F et al (2013) Evaluation of the prognostic role of pSTAT3 expression in temporal bone squamous cell carcinoma. Otol Neurotol 34:1476–1482
Marioni G, Zanoletti E, Lovato A et al (2015) Relaxin-2 expression in temporal bone carcinoma. Eur Arch Otorhinolaryngol 272:3225–3232
Bhatt AN, Mathur R, Farooque A, Verma A, Dwarakanath BS (2010) Cancer biomarkers—current perspectives. Indian J Med Res 132:129–149
Zur Hausen H (2002) Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2:342–350
Abogunrin S, Di Tanna GL, Keeping S, Carroll S, Iheanacho I (2014) Prevalence of human papillomavirus in head and neck cancers in European populations: a meta-analysis. BMC Cancer 14:968
Masterson L, Moualed D, Liu ZW et al (2014) De-escalation treatment protocols for humanpapillomavirus-associated oropharyngeal squamous cell carcinoma: a systematic review and meta-analysis of current clinical trials. Eur J Cancer 50:2636–2648
Cappellesso R, Marioni G, Crescenzi M et al (2015) The prognostic role of the epithelial-mesenchymal transition markers E-cadherin and slug in laryngeal squamous cell carcinoma. Histopathology 67:491–500
Sugimoto H, Ito M, Hatano M, Kondo S, Suzuki S, Yoshizaki T (2011) Roles of epithelial-mesenchymal transition in squamous cell carcinoma of the temporal bone. Otol Neurotol 32:483–487
Lionello M, Staffieri A, Marioni G (2012) Potential prognostic and therapeutic role for angiogenesis markers in laryngeal carcinoma. Acta Otolaryngol 132:574–582
Marioni G, D’Alessandro E, Giacomelli L, Staffieri A (2010) CD105 is a marker of tumour vasculature and a potential target for the treatment of head and neck squamous cell carcinoma. J Oral Pathol Med 39:361–367
Fonsatti E, Maio M (2004) Highlights on endoglin (CD105): from basic findings towards clinical application in human cancer. J Transl Med 2:18
Takahashi C, Sheng Z, Horan TP et al (1998) Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane- anchored glycoprotein RECK. Proc Natl Acad Sci USA 95:13221–13226
Liu X, Wang W, Chen J, Chen C, Zhou J, Cao L (2012) Expression of reversion-inducing cysteine-rich protein with kazal motifs and matrix metalloproteinase 9 in middle ear squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec 74:16–21
Marioni G, Staffieri C, Staffieri A, De Filippis C, Blandamura S (2009) MASPIN tumour-suppressing activity in head and neck squamous cell carcinoma: emerging evidence and therapeutic perspectives. Acta Otolaryngol 129:476–480
Bailey CM, Khalkhali-Ellis Z, Seftor EA, Hendrix MJ (2006) Biological functions of maspin. J Cell Physiol 209:617–624
Beltran A, Parikh S, Liu Y et al (2007) Re-activation of a dormant tumor suppressor gene MASPIN by designed transcription factors. Oncogene 26:2791–2798
Bodenstine TM, Seftor RE, Khalkhali-Ellis Z, Seftor EA, Pemberton PA, Hendrix MJ (2012) Maspin: molecular mechanisms and therapeutic implications. Cancer Metastasis Rev 31:529–551
Xu X, Kasembeli MM, Jiang X, Tweardy BJ, Tweardy DJ (2009) Chemical probes that competitively and selectively inhibit Stat3 activation. PLoS One 4:e4783
Zanoletti E, Marioni G, Stritoni P et al (2014) Temporal bone squamous cell carcinoma: analyzing prognosis with univariate and multivariate models. Laryngoscope 124:1192–1198
Facciolli A, Ferlin A, Gianesello L, Pepe A, Foresta C (2009) Role of relaxin in human osteoclastogenesis. Ann N Y Acad Sci 1160:221–225
Ma J, Niu M, Yang W, Zang L, Xi Y (2013) Role of relaxin-2 in human primary osteosarcoma. Cancer Cell Int 13:59
Ferlin A, Pepe A, Facciolli A, Gianesello L, Foresta C (2010) Relaxin stimulates osteoclast differentiation and activation. Bone 46:504–513
Marioni G, D’Alessandro E, Giacomelli L et al (2006) Maspin nuclear localization is related to reduced density of tumour-associated microvessels in laryngeal carcinoma. Anticancer Res 26:4927–4932
Lovato A, Lionello M, Staffieri A, Blandamura S, Tealdo G, Giacomelli L, Staffieri C, Marioni G (2015) A higher angiogenin expression is associated with a nonnuclear maspin location in laryngeal carcinoma. Clin Exp Otorhinolaryngol 8:268–274
http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-March-2009/
Stell PM, Mc Cormick MS (1985) Carcinoma of the external auditory meatus and middle ear: prognostic factors and a suggested staging system. J Laryngol Otol 99:847–850
Acknowledgments
This study was partly supported by Grant No. 60A07-8485/13 (G. Marioni) from the University of Padova, Padova, Italy. The authors thank Frances Coburn for correcting the English version of this paper.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
None.
Rights and permissions
About this article
Cite this article
Marioni, G., Martini, A., Favaretto, N. et al. Temporal bone carcinoma: a first glance beyond the conventional clinical and pathological prognostic factors. Eur Arch Otorhinolaryngol 273, 2903–2910 (2016). https://doi.org/10.1007/s00405-015-3811-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00405-015-3811-6