Skip to main content

Advertisement

SpringerLink
Log in

The prognostic significance of β-catenin, cyclin D1 and PIN1 in minor salivary gland carcinoma: β-catenin predicts overall survival

  • Head and Neck
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Minor salivary gland carcinoma is a rare and heterogeneous type of cancer. Molecular prognostic and predictive markers are sparse. The aim of this study was to identify new prognostic and predictive markers in minor salivary gland carcinoma. 50 tissue samples of carcinomas of the minor salivary glands (adenoid cystic carcinoma n = 23, mucoepidermoid carcinoma n = 12, adenocarcinoma n = 10, carcinoma ex pleomorphic adenoma n = 2, salivary duct carcinoma n = 1, clear cell carcinoma n = 1, basal cell carcinoma n = 1) were immunohistochemically stained for β-catenin, cyclin D1 and PIN1. Expression patterns were analyzed and correlated to clinical outcome of 37 patients with complete clinical data. High expression of membranous β-catenin was linked to significantly better overall survival in patients with adenoid cystic carcinoma (log rank test, χ 2 = 13.3, p = .00397, Bonferroni corrected p = .024). PIN1 and cyclin D1 did not show any significant correlation to patients’ clinical outcome. Expression of β-catenin in adenoid cystic carcinoma of the minor salivary glands significantly correlates with better overall survival. Hence, evaluation of β-catenin might serve as a clinical prognostic marker.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Barnes L, Eveson JW, Reichart P, Sidransky D (2005) World Health Organization classification of tumors. Pathology and genetics of head and neck tumors. IARC Press, Lyon, pp 209–281

    Google Scholar 

  2. Vander Poorten VL, Balm AJ, Hilgers FJ et al (2000) Stage as major long term outcome predictor in minor salivary gland carcinoma. Cancer 89:1195–1204

    Article  CAS  PubMed  Google Scholar 

  3. Lopes MA, Santos GC, Kowalski LP (1998) Multivariate survival analysis of 128 cases of oral cavity minor salivary gland carcinomas. Head Neck 20:699–706

    Article  CAS  PubMed  Google Scholar 

  4. Jones AS, Beasley NJ, Houghton DJ et al (1998) Tumours of the minor salivary glands. Clin Otolaryngol Allied Sci 23:27–33

    Article  CAS  PubMed  Google Scholar 

  5. Carrillo JF, Maldonado F, Carrillo LC et al (2011) Prognostic factors in patients with minor salivary gland carcinoma of the oral cavity and oropharynx. Head Neck 33:1406–1412. doi:10.1002/hed.21641

    Article  PubMed  Google Scholar 

  6. Beckhardt RN, Weber RS, Zane R et al (1995) Minor salivary gland tumors of the palate: clinical and pathologic correlates of outcome. Laryngoscope 105:1155–1160. doi:10.1288/00005537-199511000-00003

    Article  CAS  PubMed  Google Scholar 

  7. Kakarala K, Bhattacharyya N (2010) Survival in oral cavity minor salivary gland carcinoma. Otolaryngol Head Neck Surg 143:122–126. doi:10.1016/j.otohns.2010.02.033

    Article  PubMed  Google Scholar 

  8. Cianchetti M, Sandow PS, Scarborough LD et al (2009) Radiation therapy for minor salivary gland carcinoma. Laryngoscope 119:1334–1338. doi:10.1002/lary.20501

    Article  PubMed  Google Scholar 

  9. Cho KJ, Lee SS, Lee YS (1999) Proliferating cell nuclear antigen and c-erbB-2 oncoprotein expression in adenoid cystic carcinomas of the salivary glands. Head Neck 21:414–419

    Article  CAS  PubMed  Google Scholar 

  10. Luukkaa H, Klemi P, Leivo I et al (2006) Prognostic significance of Ki-67 and p53 as tumor markers in salivary gland malignancies in Finland: an evaluation of 212 cases. Acta Oncol 45:669–675. doi:10.1080/02841860500543208

    Article  PubMed  Google Scholar 

  11. Ettl T, Schwarz S, Kleinsasser N et al (2008) Overexpression of EGFR and absence of C-KIT expression correlate with poor prognosis in salivary gland carcinomas. Histopathology 53:567–577. doi:10.1111/j.1365-2559.2008.03159.x

    Article  CAS  PubMed  Google Scholar 

  12. Stenner M, Klussmann JP (2009) Current update on established and novel biomarkers in salivary gland carcinoma pathology and the molecular pathways involved. Eur Arch Otorhinolaryngol 266:333–341. doi:10.1007/s00405-008-0882-7

    Article  PubMed  Google Scholar 

  13. Behrens J, von Kries JP, Kühl M et al (1996) Functional interaction of beta-catenin with the transcription factor LEF-1. Nature 382:638–642. doi:10.1038/382638a0

    Article  CAS  PubMed  Google Scholar 

  14. Rao TP, Kühl M (2010) An updated overview on Wnt signaling pathways: a prelude for more. Circ Res 106:1798–1806. doi:10.1161/CIRCRESAHA.110.219840

    Article  CAS  PubMed  Google Scholar 

  15. Morin PJ, Sparks AB, Korinek V et al (1997) Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 275:1787–1790

    Article  CAS  PubMed  Google Scholar 

  16. Retera JM, Leers MP, Sulzer MA, Theunissen PH (1998) The expression of beta-catenin in non-small-cell lung cancer: a clinicopathological study. J Clin Pathol 51:891–894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lin SY, Xia W, Wang JC et al (2000) Beta-catenin, a novel prognostic marker for breast cancer: its roles in cyclin D1 expression and cancer progression. Proc Natl Acad Sci USA 97:4262–4266. doi:10.1073/pnas.060025397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yang F, Zeng Q, Yu G et al (2006) Wnt/beta-catenin signaling inhibits death receptor-mediated apoptosis and promotes invasive growth of HNSCC. Cell Signal 18:679–687. doi:10.1016/j.cellsig.2005.06.015

    Article  CAS  PubMed  Google Scholar 

  19. Zhou C-X, Gao Y (2006) Aberrant expression of beta-catenin, Pin1 and cyclin D1 in salivary adenoid cystic carcinoma: relation to tumor proliferation and metastasis. Oncol Rep 16:505–511

    CAS  PubMed  Google Scholar 

  20. Shieh Y-S, Chang L-C, Chiu K-C et al (2003) Cadherin and catenin expression in mucoepidermoid carcinoma: correlation with histopathologic grade, clinical stage, and patient outcome. J Oral Pathol Med 32:297–304

    Article  PubMed  Google Scholar 

  21. Shtutman M, Zhurinsky J, Simcha I et al (1999) The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci USA 96:5522–5527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Khramtsov AI, Khramtsova GF, Tretiakova M et al (2010) Wnt/beta-catenin pathway activation is enriched in basal-like breast cancers and predicts poor outcome. Am J Pathol 176:2911–2920. doi:10.2353/ajpath.2010.091125

    Article  PubMed  PubMed Central  Google Scholar 

  23. Zhao J, Li L, Wei S et al (2012) Clinicopathological and prognostic role of cyclin D1 in esophageal squamous cell carcinoma: a meta-analysis. Dis Esophagus 25:520–526. doi:10.1111/j.1442-2050.2011.01278.x

    Article  CAS  PubMed  Google Scholar 

  24. Nakashima M, Meirmanov S, Naruke Y et al (2004) Cyclin D1 overexpression in thyroid tumours from a radio-contaminated area and its correlation with Pin1 and aberrant beta-catenin expression. J Pathol 202:446–455. doi:10.1002/path.1534

    Article  CAS  PubMed  Google Scholar 

  25. Rasamny JJ, Allak A, Krook KA et al (2012) Cyclin D1 and FADD as biomarkers in head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg 146:923–931. doi:10.1177/0194599811435052

    Article  PubMed  Google Scholar 

  26. Higuchi E, Oridate N, Homma A et al (2007) Prognostic significance of cyclin D1 and p16 in patients with intermediate-risk head and neck squamous cell carcinoma treated with docetaxel and concurrent radiotherapy. Head Neck 29:940–947. doi:10.1002/hed.20632

    Article  PubMed  Google Scholar 

  27. Ryo A, Nakamura M, Wulf G et al (2001) Pin1 regulates turnover and subcellular localization of beta-catenin by inhibiting its interaction with APC. Nat Cell Biol 3:793–801. doi:10.1038/ncb0901-793

    Article  CAS  PubMed  Google Scholar 

  28. Tsuchiya R, Yamamoto G, Nagoshi Y et al (2004) Expression of adenomatous polyposis coli (APC) in tumorigenesis of human oral squamous cell carcinoma. Oral Oncol 40:932–940. doi:10.1016/j.oraloncology.2004.04.011

    Article  CAS  PubMed  Google Scholar 

  29. Fukuchi M, Fukai Y, Kimura H et al (2006) Prolyl isomerase Pin1 expression predicts prognosis in patients with esophageal squamous cell carcinoma and correlates with cyclin D1 expression. Int J Oncol 29:329–334

    CAS  PubMed  Google Scholar 

  30. Wulf GM, Ryo A, Wulf GG et al (2001) Pin1 is overexpressed in breast cancer and cooperates with Ras signaling in increasing the transcriptional activity of c-Jun towards cyclin D1. EMBO J 20:3459–3472. doi:10.1093/emboj/20.13.3459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lill C, Schneider S, Pammer J et al (2011) Significant correlation of peptidyl-prolyl isomerase overexpression in Merkel cell carcinoma with overall survival of patients. Head Neck 33:1294–1300. doi:10.1002/hed.21596

    Article  PubMed  Google Scholar 

  32. Toyoda M, Kaira K, Shino M et al (2014) CD98 as a novel prognostic indicator for patients with stage III/IV hypopharyngeal squamous cell carcinoma. Head Neck. doi:10.1002/hed.23797

    PubMed  Google Scholar 

  33. Lill C, Schneider S, Seemann R et al (2013) Correlation of β-catenin, but not PIN1 and cyclin D1, overexpression with disease-free and overall survival in patients with cancer of the parotid gland. Head Neck. doi:10.1002/hed.23546

    Google Scholar 

  34. Murakami N, Mori T, Yoshimoto S et al (2014) Expression of EpCAM and prognosis in early-stage glottic cancer treated by radiotherapy. Laryngoscope 124:E431–E436. doi:10.1002/lary.24839

    Article  PubMed  Google Scholar 

  35. Marcinow A, Ozer E, Teknos T et al (2013) Clinicopathologic predictors of recurrence and overall survival in adenoid cystic carcinoma of the head and neck: a single institutional experience at a tertiary care center. Head Neck. doi:10.1002/hed.23523

    Google Scholar 

  36. Loh KS, Barker E, Bruch G et al (2009) Prognostic factors in malignancy of the minor salivary glands. Head Neck 31:58–63. doi:10.1002/hed.20924

    Article  PubMed  Google Scholar 

  37. Brunner M, Koperek O, Wrba F et al (2012) HPV infection and p16 expression in carcinomas of the minor salivary glands. Eur Arch Otorhinolaryngol 269:2265–2269. doi:10.1007/s00405-011-1894-2

    Article  PubMed  Google Scholar 

  38. Larsen SR, Bjørndal K, Godballe C, Krogdahl A (2012) Prognostic significance of Ki-67 in salivary gland carcinomas. J Oral Pathol Med 41:598–602. doi:10.1111/j.1600-0714.2012.01148.x

    Article  PubMed  Google Scholar 

  39. Greer RO, Said S, Shroyer KR et al (2007) Overexpression of cyclin D1 and cortactin is primarily independent of gene amplification in salivary gland adenoid cystic carcinoma. Oral Oncol 43:735–741. doi:10.1016/j.oraloncology.2006.09.007

    Article  CAS  PubMed  Google Scholar 

  40. Yasumatsu R, Kuratomi Y, Nakashima T et al (2004) Cyclin D1 expression does not effect cell proliferation in adenoid cystic carcinoma of the salivary gland. Eur Arch Otorhinolaryngol 261:526–530. doi:10.1007/s00405-003-0724-6

    Article  PubMed  Google Scholar 

  41. Shiratsuchi H, Nakashima T, Hirakawa N et al (2007) beta-Catenin nuclear accumulation in head and neck mucoepidermoid carcinoma: its role in cyclin D1 overexpression and tumor progression. Head Neck 29:577–584. doi:10.1002/hed.20583

    Article  PubMed  Google Scholar 

  42. Lee C-H, Hung Y-J, Lin C-Y et al (2010) Loss of SFRP1 expression is associated with aberrant beta-catenin distribution and tumor progression in mucoepidermoid carcinoma of salivary glands. Ann Surg Oncol 17:2237–2246. doi:10.1245/s10434-010-0961-z

    Article  PubMed  Google Scholar 

  43. Chandrashekar C, Angadi PV, Krishnapillai R (2011) β-Catenin expression in benign and malignant salivary gland tumors. Int J Surg Pathol 19:433–440. doi:10.1177/1066896909346366

    Article  CAS  PubMed  Google Scholar 

  44. Daa T, Kaku N, Kashima K et al (2005) Expression of beta-catenin, E-cadherin and cyclin D1 in adenoid cystic carcinoma of the salivary gland. J Exp Clin Cancer Res 24:83–87

    CAS  PubMed  Google Scholar 

  45. Furuse C, Cury PR, Altemani A et al (2006) Beta-catenin and E-cadherin expression in salivary gland tumors. Int J Surg Pathol 14:212–217. doi:10.1177/1066896906290652

    Article  CAS  PubMed  Google Scholar 

  46. Rizzardi AE, Johnson AT, Vogel RI et al (2012) Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring. Diagn Pathol 7:42. doi:10.1186/1746-1596-7-42

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria

    Sven Schneider, Dietmar Thurnher, Markus Brunner, Lorenz Kadletz, Gregor Heiduschka & Claudia Lill

  2. Department of Cranio-, Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria

    Rudolf Seemann

  3. Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

    Bahil Ghanim

  4. Department of Pathology, Medical University of Vienna, Vienna, Austria

    Klaus Aumayr

Authors
  1. Sven Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dietmar Thurnher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rudolf Seemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Markus Brunner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lorenz Kadletz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bahil Ghanim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Klaus Aumayr
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gregor Heiduschka
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Claudia Lill
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gregor Heiduschka.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schneider, S., Thurnher, D., Seemann, R. et al. The prognostic significance of β-catenin, cyclin D1 and PIN1 in minor salivary gland carcinoma: β-catenin predicts overall survival. Eur Arch Otorhinolaryngol 273, 1283–1292 (2016). https://doi.org/10.1007/s00405-015-3609-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-015-3609-6

Keywords

Search

Navigation