Advertisement

European Archives of Oto-Rhino-Laryngology

, Volume 275, Issue 5, pp 1289–1300 | Cite as

Expression of hormone receptors in oropharyngeal squamous cell carcinoma

  • Hesham Mohamed
  • Katri Aro
  • Lauri Jouhi
  • Antti Mäkitie
  • Satu Remes
  • Caj Haglund
  • Timo Atula
  • Jaana Hagström
Head and Neck

Abstract

Objectives

Hormone receptors play an important role in many types of cancers. Alongside factors associated with human papillomavirus (HPV) infection, hormonal receptors may impact the tumorigenesis of oropharyngeal cancer.

Materials and methods

This study consists of 199 consecutive oropharyngeal squamous cell carcinoma (OPSCC) patients diagnosed and treated with a curative intent. We examined androgen (AR), estrogen (ER; both alpha and beta), and progesterone receptor (PR) expressions using immunohistochemistry comparing tumor and patient characteristics.

Results

AR was expressed in 16%, PR in 27% and ER-beta in 63% of the tumors. HPV- and p16-positive tumors expressed more AR and less PR than their negative counterparts. High PR expression was associated with poor disease-specific and locoregional recurrence-free survival.

Conclusion

AR, PR, and ER-beta are expressed in OPSCC, and AR and PR expressions are associated with HPV and p16 status. Furthermore, PR appears to have prognostic significance. This may allow us to investigate the role of anti-hormone receptors in the treatment of OPSCC.

Keywords

Oropharynx Human papillomavirus (HPV) Androgen receptor Estrogen receptor Progesterone receptor 

Notes

Funding

This work was supported by the Helsinki University Hospital Research Funds, the Sigrid Jusélius Foundation, the Otorhinolaryngology Research Foundation, Finnish Dental Association, Apollonia, and Libyan Ministry of Higher Education and Scientific Research.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The project is part of a larger research project regarding oropharyngeal cancer at the Dept. of Otorhinolaryngology Head and Neck Surgery (HUCH), and an institutional review board approval was obtained from the Research Ethics Committee of the Helsinki University Hospital (HUS). In addition, a hospital study permission was granted (Dnro179/13/03/02/2013). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

References

  1. 1.
    Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363(1):24–35.  https://doi.org/10.1056/NEJMoa0912217 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Fakhry C, Zhang Q, Nguyen-Tan PF, Rosenthal D, El-Naggar A, Garden AS, Soulieres D, Trotti A, Avizonis V, Ridge JA, Harris J, Le QT, Gillison M (2014) Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma. J Clin Oncol 32(30):3365–3373.  https://doi.org/10.1200/JCO.2014.55.1937 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Guo T, Qualliotine JR, Ha PK, Califano JA, Kim Y, Saunders JR, Blanco RG, D’Souza G, Zhang Z, Chung CH, Kiess A, Gourin CG, Koch W, Richmon JD, Agrawal N, Eisele DW, Fakhry C (2015) Surgical salvage improves overall survival for patients with HPV-positive and HPV-negative recurrent locoregional and distant metastatic oropharyngeal cancer. Cancer 121(12):1977–1984.  https://doi.org/10.1002/cncr.29323 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (2017) WHO classification of head and neck tumours, vol 9, 4th edn. Lyon, pp 134–138Google Scholar
  5. 5.
    Amini A, Jasem J, Jones BL, Robin TP, McDermott JD, Bhatia S, Raben D, Jimeno A, Bowles DW, Karam SD (2016) Predictors of overall survival in human papillomavirus-associated oropharyngeal cancer using the national cancer data base. Oral oncol 56:1–7CrossRefPubMedGoogle Scholar
  6. 6.
    Nasman A, Attner P, Hammarstedt L, Du J, Eriksson M, Giraud G, Ahrlund-Richter S, Marklund L, Romanitan M, Lindquist D, Ramqvist T, Lindholm J, Sparen P, Ye W, Dahlstrand H, Munck-Wikland E, Dalianis T (2009) Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer 125(2):362–366.  https://doi.org/10.1002/ijc.24339 CrossRefPubMedGoogle Scholar
  7. 7.
    Laco J, Vosmikova H, Novakova V, Celakovsky P, Dolezalova H, Tucek L, Nekvindova J, Vosmik M, Cermakova E, Ryska A (2011) The role of high-risk human papillomavirus infection in oral and oropharyngeal squamous cell carcinoma in non-smoking and non-drinking patients: a clinicopathological and molecular study of 46 cases. Virchows Arch 458(2):179–187CrossRefPubMedGoogle Scholar
  8. 8.
    Henderson BE, Feigelson HS (2000) Hormonal carcinogenesis. Carcinogenesis 21(3):427–433CrossRefPubMedGoogle Scholar
  9. 9.
    Narod SA, Sopik V, Sun P (2017) Which women decide to take tamoxifen? Breast Cancer Res Treat.  https://doi.org/10.1007/s10549-017-4226-4 PubMedCentralGoogle Scholar
  10. 10.
    Blesa J, Candel VA, Marco VG, Giner-Bosch V, Pulla MP, Canales J (2010) Experience with fulvestrant acetate in castration-resistant prostate cancer patients. Ann Oncol 21(5):1131–1132CrossRefGoogle Scholar
  11. 11.
    Ojanotko-Harri A, Forssell H, Laine M, Hurttia H, Bläuer M, Tuohimaa P (1992) Immunohistochemical detection of androgen receptors in human oral mucosa. Arch Oral Biol 37(6):511–514CrossRefPubMedGoogle Scholar
  12. 12.
    Ruizeveld de Winter J, Trapman J, Vermey M, Mulder E, Zegers ND, van der Kwast TH (1991) Androgen receptor expression in human tissues: an immunohistochemical study. J Histochem Cytochem 39(7):927–936CrossRefPubMedGoogle Scholar
  13. 13.
    Rades D, Seibold ND, Schild SE, Bruchhage KL, Gebhard MP, Noack F (2013) Androgen receptor expression: prognostic value in locally advanced squamous cell carcinoma of the head and neck. Strahlenther Onkol 189(10):849–855.  https://doi.org/10.1007/s00066-013-0389-z CrossRefPubMedGoogle Scholar
  14. 14.
    Gonzalez LO, Corte MD, Vazquez J, Junquera S, Sanchez R, Alvarez AC, Rodriguez JC, Lamelas ML, Vizoso FJ (2008) Androgen receptor expresion in breast cancer: relationship with clinicopathological characteristics of the tumors, prognosis, and expression of metalloproteases and their inhibitors. BMC Cancer 8:149.  https://doi.org/10.1186/1471-2407-8-149 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Luk PP, Weston JD, Yu B, Selinger CI, Ekmejian R, Eviston TJ, Lum T, Gao K, Boyer M, O'Toole SA, Clark FR, Gupta R (2016) Salivary duct carcinoma: clinicopathologic features, morphologic spectrum, and somatic mutations. Head Neck 38(Suppl 1):E1838–E1847.  https://doi.org/10.1002/hed.24332
  16. 16.
    Williams L, Thompson LD, Seethala RR, Weinreb I, Assaad AM, Tuluc M, Din NU, Purgina B, Lai C, Griffith CC (2015) Salivary duct carcinoma: the predominance of apocrine morphology, prevalence of histologic variants, and androgen receptor expression. Am J Surg Pathol 39(5):705–713CrossRefPubMedGoogle Scholar
  17. 17.
    Wu TF, Luo FJ, Chang YL, Huang CM, Chiu WJ, Weng CF, Hsu YK, Yuan TC (2015) The oncogenic role of androgen receptors in promoting the growth of oral squamous cell carcinoma cells. Oral Dis 21(3):320–327CrossRefPubMedGoogle Scholar
  18. 18.
    Valimaa H, Savolainen S, Soukka T, Silvoniemi P, Makela S, Kujari H, Gustafsson J-A, Laine M (2004) Estrogen receptor-beta is the predominant estrogen receptor subtype in human oral epithelium and salivary glands. J Endocrinol 180(1):55–62CrossRefPubMedGoogle Scholar
  19. 19.
    Colella G, Izzo G, Carinci F, Campisi G, Lo Muzio L, D’Amato S, Mazzotta M, Cannavale R, Ferrara D, Minucci S (2011) Expression of sexual hormones receptors in oral squamous cell carcinoma. Int J Immunopathol Pharmacol 24(2_suppl):129–132CrossRefPubMedGoogle Scholar
  20. 20.
    Nehse G, Tunn S (1994) Androgen and progesterone receptors in oral carcinoma. J Cranio-Maxillofac Surg 22(2):114–119CrossRefGoogle Scholar
  21. 21.
    Bianchini C, Pastore A, Pelucchi S, Torreggiani E, Lambertini E, Marchesi E, Magri E, Frasson C, Querzoli P, Piva R (2008) Sex hormone receptor levels in laryngeal carcinoma: a comparison between protein and RNA evaluations. Eur Arch Otorhinolaryngol 265(9):1089–1094CrossRefPubMedGoogle Scholar
  22. 22.
    Virolainen E, Tuohimaa P, Aitasalo K, Kyttä J, Vanharanta-Hiltunen R (1986) Steroid hormone receptors in laryngeal carcinoma. Otolaryngol Head Neck Surg 94(4):512–517CrossRefPubMedGoogle Scholar
  23. 23.
    Berg NJ, Colvard DS, Neel HB III, Weiland LH, Spelsberg TC (1989) Progesterone receptors in carcinomas of the upper aerodigestive tract. Otolaryngol Head Neck Surg 101(5):527–536CrossRefPubMedGoogle Scholar
  24. 24.
    James D. Brierley MKG, Christian W (2016) TNM classification of malignant tumours, 8th edn. John Wiley, New YorkGoogle Scholar
  25. 25.
    Jouhi L, Mohamed H, Makitie A, Remes SM, Haglund C, Atula T, Hagstrom J (2017) Toll-like receptor 5 and 7 expression may impact prognosis of HPV-positive oropharyngeal squamous cell carcinoma patients. Cancer Immunol Immunother.  https://doi.org/10.1007/s00262-017-2054-3 PubMedGoogle Scholar
  26. 26.
    Makinen LK, Hayry V, Atula T, Haglund C, Keski-Santti H, Leivo I, Makitie A, Passador-Santos F, Bockelman C, Salo T, Sorsa T, Hagstrom J (2012) Prognostic significance of matrix metalloproteinase-2, -8, -9, and – 13 in oral tongue cancer. J Oral Pathol Med 41(5):394–399.  https://doi.org/10.1111/j.1600-0714.2011.01110.x CrossRefPubMedGoogle Scholar
  27. 27.
    Bekkers R, van der Avoort I, Melchers W, Bulten J, de Wilde P, Massuger L (2004) Down regulation of estrogen receptor expression is an early event in human papillomavirus infected cervical dysplasia. Eur J Gynaecol Oncol 26(4):376–382Google Scholar
  28. 28.
    Haapaniemi A, Koivunen P, Saarilahti K, Kinnunen I, Laranne J, Aaltonen LM, Närkiö M, Lindholm P, Grénman R, Mäkitie A (2016) Laryngeal cancer in Finland: A 5-year follow-up study of 366 patients. Head Neck 38(1):36–43CrossRefPubMedGoogle Scholar
  29. 29.
    Burke SC, Smith KV, Sharmin S, Winkelman C (2014) Prevalence of risk factors related to head and neck squamous cell carcinoma (HNSCC) among college students. Cancer Oncol Res 2(1):7–16Google Scholar
  30. 30.
    Marocchio LS, Giudice F, Corrêa L, Pinto DDS Jr, de Sousa SOM (2013) Oestrogens and androgen receptors in oral squamous cell carcinoma. Acta Odontol Scand 71(6):1513–1519CrossRefPubMedGoogle Scholar
  31. 31.
    Goulioumis AK, Varakis J, Goumas P, Papadaki H (2011) Androgen receptor in laryngeal carcinoma: could there be an androgen-refractory tumor? ISRN Oncol 2011:180518.  https://doi.org/10.5402/2011/180518
  32. 32.
    Zhang Y, Pan T, Zhong X, Cheng C (2015) Androgen receptor promotes esophageal cancer cell migration and proliferation via matrix metalloproteinase 2. Tumour Biol 36(8):5859–5864.  https://doi.org/10.1007/s13277-015-3257-x CrossRefPubMedGoogle Scholar
  33. 33.
    Jia M, Andreassen T, Jensen L, Bathen TF, Sinha I, Gao H, Zhao C, Haldosen L-A, Cao Y, Girnita L (2016) Estrogen receptor α promotes breast cancer by reprogramming choline metabolism. Cancer Res 76(19):5634–5646CrossRefPubMedGoogle Scholar
  34. 34.
    López-Romero R, Garrido-Guerrero E, Rangel-López A, Manuel-Apolinar L, Piña-Sánchez P, Lazos-Ochoa M, Mantilla-Morales A, Bandala C, Salcedo M (2013) The cervical malignant cells display a down regulation of ER-α but retain the ER-β expression. Int J Clin Exp Pathol 6(8):1594–1602PubMedPubMedCentralGoogle Scholar
  35. 35.
    Ishida H, Wada K, Masuda T, Okura M, Kohama K, Sano Y, Nakajima A, Kogo M, Kamisaki Y (2007) Critical role of estrogen receptor on anoikis and invasion of squamous cell carcinoma. Cancer Sci 98(5):636–643.  https://doi.org/10.1111/j.1349-7006.2007.00437.x CrossRefPubMedGoogle Scholar
  36. 36.
    Gingelmaier A, Gutsche S, Mylonas I, Shabani N, Kuhn C, Kunze S, Jeschke U, Friese K (2007) Expression of HPV, steroid receptors (ERα, ERβ, PR-A and PR-B) and inhibin/activin subunits (α, βA and βB) in adenosquamous endometrial carcinoma. Anticancer Res 27(4A):2011–2017PubMedGoogle Scholar
  37. 37.
    Grimm M, Biegner T, Teriete P, Hoefert S, Krimmel M, Munz A, Reinert S (2016) Estrogen and progesterone hormone receptor expression in oral cavity cancer. Med Oral Patol Oral y Cir Bucal 21(5):e554Google Scholar
  38. 38.
    Boukari R, Marcouiller F, Joseph V (2015) Relative contribution of nuclear and membrane progesterone receptors in respiratory control. In: Arterial chemoreceptors in physiology and pathophysiology. Springer, Cham, pp 261–267CrossRefGoogle Scholar
  39. 39.
    Buttarelli M, Mascilini F, Zannoni GF, Ciucci A, Martinelli E, Filippetti F, Scambia G, Ferrandina G, Gallo D (2017) Hormone receptor expression profile of low-grade serous ovarian cancers. Gynecol Oncol 145(2):352–360CrossRefPubMedGoogle Scholar
  40. 40.
    D’Amato NC, Gordon MA, Babbs B, Spoelstra NS, Butterfield KTC, Torkko KC, Phan VT, Barton VN, Rogers TJ, Sartorius CA (2016) Cooperative dynamics of AR and ER activity in breast cancer. Mol Cancer Res 14(11):1054–1067CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Li R, Wheeler T, Dai H, Frolov A, Thompson T, Ayala G (2004) High level of androgen receptor is associated with aggressive clinicopathologic features and decreased biochemical recurrence-free survival in prostate: cancer patients treated with radical prostatectomy. Am J Surg Pathol 28(7):928–934CrossRefPubMedGoogle Scholar
  42. 42.
    Kauffman EC, Robinson BD, Downes MJ, Powell LG, Lee MM, Scherr DS, Gudas LJ, Mongan NP (2011) Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer. Mol Carcinog 50(12):931–944CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Wikström P, Marusic J, Stattin P, Bergh A (2009) Low stroma androgen receptor level in normal and tumor prostate tissue is related to poor outcome in prostate cancer patients. Prostate 69(8):799–809CrossRefPubMedGoogle Scholar
  44. 44.
    Magri F, Capelli V, Rotondi M, Leporati P, La Manna L, Ruggiero R, Malovini A, Bellazzi R, Villani L, Chiovato L (2012) Expression of estrogen and androgen receptors in differentiated thyroid cancer: an additional criterion to assess the patient’s risk. Endocr Relat Cancer 19(4):463–471CrossRefPubMedGoogle Scholar
  45. 45.
    Lukits J, Remenar E, Rásó E, Ladányi A, Kásler M, Tímár J (2007) Molecular identification, expression and prognostic role of estrogen-and progesterone receptors in head and neck cancer. Int J Oncol 30(1):155–160PubMedGoogle Scholar
  46. 46.
    Chen R, Yu Y, Dong X (2017) Progesterone receptor in the prostate: A potential suppressor for benign prostatic hyperplasia and prostate cancer. J Steroid Biochem Mol Biol 166:91–96CrossRefPubMedGoogle Scholar
  47. 47.
    Carey T, Grenman R, Virolainen E, Shapira A (1987) In vitro effects of tamoxifen on UM-SCC head and neck cancer cell lines: Correlation with the estrogen and progesterone receptor content. Int J Cancer 39(1):77–81CrossRefPubMedGoogle Scholar
  48. 48.
    Hagedorn HG, Nerlich AG (2002) Analysis of sex-hormone-receptor expression in laryngeal carcinoma. Eur Arch Oto-Rhino-Laryngol. 259 (4):205–210CrossRefGoogle Scholar
  49. 49.
    Scambia G, Panici PB, Battaglia F, Ferrandina G, Almadori G, Paludetti G, Maurizi M, Mancuso S (1991) Receptors for epidermal growth factor and steroid hormones in primary laryngeal tumors. Cancer 67(5):1347–1351CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PathologyUniversity of Helsinki, HusLab and Helsinki University HospitalHelsinkiFinland
  2. 2.Department of HistologyOmar Al-Mukhtar UniversityAlBaydaLibya
  3. 3.Department of Otorhinolaryngology, Head and Neck SurgeryUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
  4. 4.Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska InstitutetKarolinska University HospitalStockholmSweden
  5. 5.Department of SurgeryUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
  6. 6.Research Programs Unit, Translational Cancer BiologyUniversity of HelsinkiHelsinkiFinland

Personalised recommendations