Head and Neck Pathology

, Volume 12, Issue 1, pp 95–104 | Cite as

Expression of Hormone Receptors and HER-2 in Benign and Malignant Salivary Gland Tumors

  • Nhu Thuy Can
  • Mark W. Lingen
  • Heather Mashek
  • James McElherne
  • Renee Briese
  • Carrie Fitzpatrick
  • Annemieke van Zante
  • Nicole A. Cipriani
Original Paper


With the advent of targeted therapies, expression of sex hormone receptors and HER-2 in salivary gland tumors (SGTs) is of clinical interest. Previous reports of estrogen (ER) and progesterone (PR) receptor expression have varied. Androgen receptor (AR) and HER-2 overexpression are frequently reported in salivary duct carcinoma (SDC), but have not been studied systematically in other SGTs. This study examines ER, PR, AR, and HER-2 expression in SGTs. Immunohistochemistry for ER, PR, AR, and HER-2 was performed on 254 SGTs (134 malignant). ER, PR, and AR expression was scored using Allred system. HER-2 expression was scored using Dako HercepTest guidelines. FISH for HER-2 amplification was performed on select cases with HER-2 overexpression (2–3+). No SGT demonstrated strong expression of ER or PR. Combined strong AR and HER-2 expression was seen in 22 carcinomas: 14/25 SDC, 3/16 poorly differentiated, two oncocytic, and one each carcinoma ex pleomorphic adenoma, squamous cell, and intraductal carcinoma. Eighteen additional high grade carcinomas had HER-2 overexpression with absent, weak, or moderate AR expression; eight high grade carcinomas had isolated strong AR expression with 0–1+ HER-2 staining. Of 15 tested cases, six demonstrated HER-2 amplification by FISH, all of which had 3+ immunoreactivity. Neither benign nor malignant SGTs had strong expression of ER or PR. None of the benign SGTs overexpressed AR or HER-2. Coexpression of AR and HER-2 should not define SDC, but immunostaining should be considered in high grade salivary carcinomas, as some show overexpression and may benefit from targeted therapy.


Salivary gland tumors Salivary duct carcinoma Hormone receptors Estrogen Progesterone Androgen HER-2 FISH 



We would like to thank the staff at the Human Tissue Resource Center at the University of Chicago, particularly Terri Li, for their assistance with this project.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

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. For this type of study formal consent is not required.


  1. 1.
    Alotaibi AM, Alqarni MA, Alnobi A, Tarakji B. Human epidermal growth factor receptor 2 (HER2/neu) in salivary gland carcinomas: a review of literature. J Clin Diagn Res. 2015;9(2):ZE04–8.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Limaye SA, Posner MR, Krane JF, Fonfria M, Lorch JH, Dillon DA, et al. Trastuzumab for the treatment of salivary duct carcinoma. Oncologist. 2013;18(3):294–300.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Masubuchi T, Tada Y, Maruya S, Osamura Y, Kamata SE, Miura K, et al. Clinicopathological significance of androgen receptor, HER2, Ki-67 and EGFR expressions in salivary duct carcinoma. Int J Clin Oncol. 2015;20(1):35–44.CrossRefPubMedGoogle Scholar
  4. 4.
    Nabili V, Tan JW, Bhuta S, Sercarz JA, Head CS. Salivary duct carcinoma: a clinical and histologic review with implications for trastuzumab therapy. Head Neck. 2007;29(10):907–12.CrossRefPubMedGoogle Scholar
  5. 5.
    Perissinotti AJ, Lee Pierce M, Pace MB, El-Naggar A, Kies MS, Kupferman M. The role of trastuzumab in the management of salivary ductal carcinomas. Anticancer Res. 2013;33(6):2587–91.PubMedGoogle Scholar
  6. 6.
    Simpson RH. Salivary duct carcinoma: new developments—morphological variants including pure in situ high grade lesions; proposed molecular classification. Head Neck Pathol. 2013;7(Suppl 1):S48–S58.CrossRefPubMedGoogle Scholar
  7. 7.
    Vidal L, Tsao MS, Pond GR, Cohen EE, Cohen RB, Chen EX, et al. Fluorescence in situ hybridization gene amplification analysis of EGFR and HER2 in patients with malignant salivary gland tumors treated with lapatinib. Head Neck. 2009;31(8):1006–12.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Yamamoto N, Minami S, Fujii M. Clinicopathologic study of salivary duct carcinoma and the efficacy of androgen deprivation therapy. Am J Otolaryngol. 2014;35(6):731–5.CrossRefPubMedGoogle Scholar
  9. 9.
    Barrera JE, Shroyer KR, Said S, Hoernig G, Melrose R, Freedman PD, et al. Estrogen and progesterone receptor and p53 gene expression in adenoid cystic cancer. Head Neck Pathol. 2008;2(1):13–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Dori S, Trougouboff P, David R, Buchner A. Immunohistochemical evaluation of estrogen and progesterone receptors in adenoid cystic carcinoma of salivary gland origin. Oral Oncol. 2000;36(5):450–3.CrossRefPubMedGoogle Scholar
  11. 11.
    Nasser SM, Faquin WC, Dayal Y. Expression of androgen, estrogen, and progesterone receptors in salivary gland tumors. Am J Clin Pathol. 2003;119(6):801–6.CrossRefPubMedGoogle Scholar
  12. 12.
    Pires FR, Perez DEDC, de Almeida OP, Kowalski LP. Estrogen receptor expression in salivary gland mucoepidermoid carcinoma and adenoid cystic carcinoma. Pathol Oncol Res. 2004;10(3):166–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Shick PC, Riordan GP, Foss RD. Estrogen and progesterone receptors in salivary gland adenoid cystic carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995;80(4):440–4.CrossRefPubMedGoogle Scholar
  14. 14.
    Butler RT, Spector ME, Thomas D, McDaniel AS, McHugh JB. An immunohistochemical panel for reliable differentiation of salivary duct carcinoma and mucoepidermoid carcinoma. Head Neck Pathol. 2014;8(2):133–40.CrossRefPubMedGoogle Scholar
  15. 15.
    Cornolti G, Ungari M, Morassi ML, Facchetti F, Rossi E, Lombardi D, et al. Amplification and overexpression of HER2/neu gene and HER2/neu protein in salivary duct carcinoma of the parotid gland. Arch Otolaryngol Head Neck Surg. 2007;133(10):1031–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Di Palma S, Simpson RH, Marchio C, Skalova A, Ungari M, Sandison A, et al. Salivary duct carcinomas can be classified into luminal androgen receptor-positive, HER2 and basal-like phenotypes. Histopathology. 2012;61(4):629–43.CrossRefPubMedGoogle Scholar
  17. 17.
    Ghazali N, Parker L, Settle K, Lubek JE. Sustained response of HER2-positive metastatic salivary adenocarcinoma, not otherwise specified, treated with trastuzumab. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;122(3):292–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Glisson B, Colevas AD, Haddad R, Krane J, El-Naggar A, Kies M, et al. HER2 expression in salivary gland carcinomas: dependence on histological subtype. Clin Cancer Res. 2004;10(3):944–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Kaidar-Person O, Billan S, Kuten A. Targeted therapy with trastuzumab for advanced salivary ductal carcinoma: case report and literature review. Med Oncol. 2012;29(2):704–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Prat A, Parera M, Reyes V, Peralta S, Cedres S, Andreu J, et al. Successful treatment of pulmonary metastatic salivary ductal carcinoma with trastuzumab-based therapy. Head Neck. 2008;30(5):680–3.CrossRefPubMedGoogle Scholar
  21. 21.
    Skalova A, Starek I, Vanecek T, Kucerova V, Plank L, Szepe P, et al. Expression of HER-2/neu gene and protein in salivary duct carcinomas of parotid gland as revealed by fluorescence in-situ hybridization and immunohistochemistry. Histopathology. 2003;42(4):348–56.CrossRefPubMedGoogle Scholar
  22. 22.
    Soper MS, Iganej S, Thompson LD. Definitive treatment of androgen receptor-positive salivary duct carcinoma with androgen deprivation therapy and external beam radiotherapy. Head Neck. 2014;36(1):E4–E7.CrossRefPubMedGoogle Scholar
  23. 23.
    Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998;11(2):155–68.PubMedGoogle Scholar
  24. 24.
    Nadji M, Gomez-Fernandez C, Ganjei-Azar P, Morales AR. Immunohistochemistry of estrogen and progesterone receptors reconsidered: experience with 5993 breast cancers. Am J Clin Pathol. 2005;123(1):21–7.CrossRefPubMedGoogle Scholar
  25. 25.
    Honma N, Horii R, Iwase T, Saji S, Younes M, Ito Y, et al. Proportion of estrogen or progesterone receptor expressing cells in breast cancers and response to endocrine therapy. Breast. 2014;23(6):754–62.CrossRefPubMedGoogle Scholar
  26. 26.
    DeRoche TC, Hoschar AP, Hunt JL. Immunohistochemical evaluation of androgen receptor, HER-2/neu, and p53 in benign pleomorphic adenomas. Arch Pathol Lab Med. 2008;132(12):1907–11.PubMedGoogle Scholar
  27. 27.
    van der Hulst RW, van Krieken JH, van der Kwast TH, Gerritsen JJ, de Jong RB, a Nijeholt AL et al. Partial remission of parotid gland carcinoma after goserelin. Lancet. 1994;344(8925):817.CrossRefPubMedGoogle Scholar
  28. 28.
    Locati LD, Quattrone P, Bossi P, Marchiano AV, Cantu G, Licitra L. A complete remission with androgen-deprivation therapy in a recurrent androgen receptor-expressing adenocarcinoma of the parotid gland. Ann Oncol. 2003;14(8):1327–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Locati LD, Perrone F, Cortelazzi B, Lo Vullo S, Bossi P, Dagrada G, et al. Clinical activity of androgen deprivation therapy in patients with metastatic/relapsed androgen receptor-positive salivary gland cancers. Head Neck. 2016;38(5):724–31.CrossRefPubMedGoogle Scholar
  30. 30.
    Jaspers HC, Verbist BM, Schoffelen R, Mattijssen V, Slootweg PJ, van der Graaf WT, et al. Androgen receptor-positive salivary duct carcinoma: a disease entity with promising new treatment options. J Clin Oncol. 2011;29(16):e473–e6.CrossRefPubMedGoogle Scholar
  31. 31.
    Haddad R, Colevas AD, Krane JF, Cooper D, Glisson B, Amrein PC, et al. Herceptin in patients with advanced or metastatic salivary gland carcinomas. A phase II study. Oral Oncol. 2003;39(7):724–7.CrossRefPubMedGoogle Scholar
  32. 32.
    Clauditz TS, Reiff M, Gravert L, Gnoss A, Tsourlakis MC, Munscher A, et al. Human epidermal growth factor receptor 2 (HER2) in salivary gland carcinomas. Pathology. 2011;43(5):459–64.CrossRefPubMedGoogle Scholar
  33. 33.
    Press MF, Sauter G, Bernstein L, Villalobos IE, Mirlacher M, Zhou JY et al. Diagnostic evaluation of HER-2 as a molecular target: an assessment of accuracy and reproducibility of laboratory testing in large, prospective, randomized clinical trials. Clin Cancer Res. 2005;11(18):6598–607.CrossRefPubMedGoogle Scholar
  34. 34.
    Sharon E, Kelly RJ, Szabo E. Sustained response of carcinoma ex pleomorphic adenoma treated with trastuzumab and capecitabine. Head Neck Oncol. 2010;2:12.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of PathologyThe University of Chicago MedicineChicagoUSA
  2. 2.Department of PathologyUniversity of California San FranciscoSan FranciscoUSA
  3. 3.Constitutional Cytogenetics and Cytogenomics, Department of PathologyThe University of Chicago MedicineChicagoUSA

Personalised recommendations