Skip to main content
SpringerLink
Log in

P-Cadherin and WNT5A expression in assessment of lymph node metastasis in oral squamous cell carcinoma

  • Original Article
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Background

Oral cancer progression is a multi-step process in which adhesion molecules play a pivotal role in the development of recurrent, invasive, and distant metastasis. The aim of this study was to adopt prognostic biomarkers to assess the lymph node metastasis of OSCC that will facilitate in deciding the treatment modality by the surgeons.

Objectives

The objectives of the study were to assess the biological behaviour of OSCC by correlating the expression levels of P-Cadherin and WNT5A immunohistochemically.

Methods

A total of 60 selected OSCCs cases (lymph node metastasis n = 30, non-metastatic n = 30) and 10 normal healthy controls were quantitatively and qualitatively analysed by immunohistochemistry for P-Cadherin and WNT5A. A survival analysis was also performed.

Results

The expression levels of P-Cadherin and WNT5A in OSCC groups were statistically significant between metastatic and non-metastatic groups (p < 0.001). P-Cadherin and WNT5A expression in metastatic (lymph node metastasis) and non-metastatic cases showed a significant correlation coefficient of 0.753 at (p < 0.01). The present study also found that the aberrant expression (high) of P-Cadherin was associated with diminished survival of patients with metastatic OSCC.

Conclusion

The present study demonstrated the aberrant expression of P-Cadherin and WNT5A could serve as important prognosticator in OSCC.

Clinical relevance

P-Cadherin and WNT5A could be used as significant predictors of disease outcome.

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

OSCC :

Oral squamous cell carcinoma

WNT5A :

Wingless-Type 5A

HNSCC :

Head and neck squamous cell carcinoma

FFPE :

Formalin-fixed paraffin-embedded

UICC :

Union for International Cancer Control

EDTA :

Ethylene diamine tetra-acetic acid

NOM :

Normal mucosa

DAB :

Diamine-benzidine

References

  1. Sathiyasekar AC, Chandrasekar P, Pakash A, Kumar KG, Jaishlal MS (2016) Overview of immunology of oral squamous cell carcinoma. J Pharm Bioallied Sci 8(Suppl 1):S8

    PubMed  PubMed Central  Google Scholar 

  2. Sklenicka S, Gardiner S, Dierks EJ, Potter BE, Bell RB (2010) Survival analysis and risk factors for recurrence in oral squamous cell carcinoma: does surgical salvage affect outcome? J Oral Maxillofac Surg 68(6):1270–1275

    Article  Google Scholar 

  3. Kim MM, Califano JA (2004) Molecular pathology of head-and-neck cancer. Int J Cancer 112(4):545–553

    Article  Google Scholar 

  4. Nguyen PT, Kudo Y, Yoshida M, Kamata N, Ogawa I, Takata T (2011) N-cadherin expression is involved in malignant behaviour of head and neck cancer in relation to epithelial-mesenchymal transition. Histol Histopathol 26(1):147

    PubMed  Google Scholar 

  5. Kupferman ME, Patel V, Sriuranpong V, Amornphimoltham P, Jasser SA, Mandal M, Zhou G, Wang J, Coombes K, Multani A, Pathak S (2007) Molecular analysis of anoikis resistance in oral cavity squamous cell carcinoma. Oral Oncol 43(5):440–454

    Article  Google Scholar 

  6. Muñoz-Guerra MF, Marazuela EG, Fernández-Contreras ME, Gamallo C (2005) P-cadherin expression reduced in squamous cell carcinoma of the oral cavity: An indicator of poor prognosis. Cancer 103(5):960–9

    Article  Google Scholar 

  7. Yamamoto E, Miyakawa A, Kohama GI (1984) Mode of invasion and lymph node metastasis in squamous cell carcinoma of the oral cavity. Head Neck Surg 6(5):938–947

    Article  Google Scholar 

  8. Mohammad DN, Garib BT, Khudeir HH, Abdul–Majeed BA. Immunohistochemical expression of P-cadherin and cortactin in oral squamous cell carcinomas

  9. Meng W, Takeichi M (2009) Adherens junction: molecular architecture and regulation. Cold Spring Harb Perspect Biol 5:a002899

    Google Scholar 

  10. Nelson WJ, Nusse R (2004) Convergence of Wnt, ß-catenin, and cadherin pathways. Science 303(5663):1483–1487

    Article  Google Scholar 

  11. Jiang WG, Sanders AJ, Katoh M, Ungefroren H, Gieseler F, Prince M, Thompson SK, Zollo M, Spano D, Dhawan P, Sliva D. Tissue invasion and metastasis: Molecular, biological and clinical perspectives. In Seminars in cancer biology 2015 Dec 1 (Vol. 35, pp. S244-S275). Academic Press

  12. Vieira AF, Paredes J (2015) P-cadherin and the journey to cancer metastasis. Mol Cancer 14(1):178

    Article  Google Scholar 

  13. McDonald SL, Silver A (2009) The opposing roles of Wnt-5a in cancer. Br J Cancer 101(2):209

    Article  Google Scholar 

  14. Prgomet Z, Andersson T, Lindberg P (2017) Higher expression of WNT 5A protein in oral squamous cell carcinoma compared with dysplasia and oral mucosa with a normal appearance. Eur J Oral Sci 125(4):237–246

    Article  Google Scholar 

  15. Qin L, Yin YT, Zheng FJ, Peng LX, Yang CF, Bao YN, Liang YY, Li XJ, Xiang YQ, Sun R, Li AH (2015) WNT5A promotes stemness characteristics in nasopharyngeal carcinoma cells leading to metastasis and tumorigenesis. Oncotarget 6(12):10239

    Article  Google Scholar 

  16. Sun L, Hu H, Peng L, Zhou Z, Zhao X, Pan J, Sun L, Yang Z, Ran Y (2011) P-cadherin promotes liver metastasis and is associated with poor prognosis in colon cancer. Am J Pathol 179(1):380–390

    Article  Google Scholar 

  17. Rasbridge SA, Gillett CE, Sampson SA, Walsh FS, Millis RR (1993) Epithelial (E-) and placentae (P-) cadherin cell adhesion molecule expression in breast carcinoma. J Pathol 169(2):245–250

    Article  Google Scholar 

  18. Palacios J, Benito N, Pizarro A, Suárez A, Espada J, Cano A, Gamallo C (1995) Anomalous expression of P-cadherin in breast carcinoma. Correlation with E-cadherin expression and pathological features. The American journal of pathology 146(3):605

    PubMed  PubMed Central  Google Scholar 

  19. Zhu N, Qin L, Luo Z, Guo Q, Yang L, Liao D (2014) Challenging role of Wnt5a and its signaling pathway in cancer metastasis. Exp Ther Med 8(1):3–8

    Article  Google Scholar 

  20. Bo H, Zhang S, Gao L, Chen Y, Zhang J, Chang X, Zhu M (2013) Upregulation of Wnt5a promotes epithelial-to-mesenchymal transition and metastasis of pancreatic cancer cells. BMC Cancer 13(1):496

    Article  Google Scholar 

  21. Shimoyama Y, Hirohashi S (1991) Expression of E-and P-cadherin in gastric carcinomas. Can Res 51(8):2185–2192

    Google Scholar 

  22. Paredes J, Albergaria A, Oliveira JT, Jerónimo C, Milanezi F, Schmitt FC (2005) P-cadherin overexpression is an indicator of clinical outcome in invasive breast carcinomas and is associated with CDH3 promoter hypomethylation. Clin Cancer Res 11(16):5869–5877

    Article  Google Scholar 

  23. Muzio LL, Campisi G, Farina A, Rubini C, Pannone G, Serpico R, Laino G, De Lillo A, Carinci F (2005) P-cadherin expression and survival rate in oral squamous cell carcinoma: an immunohistochemical study. BMC Cancer 5(1):63

    Article  Google Scholar 

  24. Bauer K, Gosau M, Reinders J, Oefner P, Reichert TE, Bauer R (2013) Presenilin 1/γ-secretase modulates P-cadherin processing and influences cell adhesion in oral squamous cell carcinoma cell lines. Carcinogenesis 34(11):2622–2628

    Article  Google Scholar 

  25. Mandeville JA, Neto BS, Vanni AJ, Smith GL, Rieger-Christ KM, Zeheb R, Loda M, Libertino JA, Summerhayes IC (2008) P-cadherin as a prognostic indicator and a modulator of migratory behaviour in bladder carcinoma cells. BJU Int 102(11):1707–1714

    Article  Google Scholar 

  26. Paredes J, Correia AL, Ribeiro AS, Milanezi F, Cameselle-Teijeiro J, Schmitt FC (2008) Breast carcinomas that co-express E-and P-cadherin are associated with p120-catenin cytoplasmic localization and poor patient survival. J Clin Pathol

  27. Noguti J, De Moura CF, De Jesus GP, Da Silva VH, Hossaka TA, Oshima CT, Ribeiro DA (2012) Metastasis from oral cancer: an overview. Cancer Genomics-Proteomics 9(5):329–335

    PubMed  Google Scholar 

  28. Bauer R, Dowejko A, Driemel O, Boberhoff AK, Reichert TE (2008) Truncated P-cadherin is produced in oral squamous cell carcinoma. FEBS J 275(16):4198–4210

    Article  Google Scholar 

  29. Peixoto TS, Gomes MC, de Castro Gomes DQ, Lima KC, Granville-Garcia AF, de Brito Costa EM (2017) Analysis of survival rates and prognostic factors among patients with oral squamous cell carcinoma. J Public Health 25(4):433–441

    Article  Google Scholar 

  30. Janot F, Klijanienko J, Russo A, Mamet JP, De Braud F, El-Naggar AK, Pignon JP, Luboinski B, Cvitkovic E (1996) Prognostic value of clinicopathological parameters in head and neck squamous cell carcinoma: a prospective analysis. Br J Cancer 73(4):531

    Article  Google Scholar 

  31. Pires FR, Ramos AB, Oliveira JB, Tavares AS, Luz PS, Santos TC (2013) Oral squamous cell carcinoma: clinicopathological features from 346 cases from a single oral pathology service during an 8-year period. J Appl Oral Sci 21(5):460–467

    Article  Google Scholar 

  32. Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS (1999) Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 341(27):2061–2067

    Article  Google Scholar 

  33. Feller LL, Khammissa RR, Kramer BB, Lemmer JJ (2013) Oral squamous cell carcinoma in relation to field precancerisation: pathobiology. Cancer Cell Int 13(1):31

    Article  Google Scholar 

  34. Abraham M, Sowmya SV, Rao RS, Haragannavar VC, Patil S, Augustine D, Nambiar S (2018) Stearoyl coenzyme A desaturase: A diagnostic and prognostic biomarker in patients with oral epithelial dysplasia and oral squamous cell carcinoma. Translational Research in Oral Oncology 3:2057178X18782512

    Article  Google Scholar 

  35. Bundgaard T, Bentzen SM, Wildt J, Sorensen FB, Søgaard H, Nielsen JE (1996) Histopathologic, stereologic, epidemiologic, and clinical parameters in the prognostic evaluation of squamous cell carcinoma of the oral cavity. Head Neck 18(2):142–152

    Article  Google Scholar 

  36. Mehta V, Yu GP, Schantz SP (2010) Population-based analysis of oral and oropharyngeal carcinoma: changing trends of histopathologic differentiation, survival and patient demographics. Laryngoscope 120(11):2203–2212

    Article  Google Scholar 

  37. Kantola S, Parikka M, Jokinen K, Hyrynkangs K, Soini Y, Alho OP, Salo T (2000) Prognostic factors in tongue cancer–relative importance of demographic, clinical and histopathological factors. Br J Cancer 83(5):614

    Article  Google Scholar 

  38. Gravdal K, Halverson OJ, Haukaas SA, Akslen LA (2007) A switch from E-cadherin to N-cadherin expression indicates epithelial to mesenchymal transition and is of strong and independent importance for the progress of prostate cancer. Clin Cancer Res 13(23):7003–7011

    Article  Google Scholar 

  39. Yi S, Yang ZL, Miao X, Zou Q, Li J, Liang L, Zeng G, Chen S (2014) N-cadherin and P-cadherin are biomarkers for invasion, metastasis, and poor prognosis of gallbladder carcinomas. Pathology-Research and Practice 210(6):363–368

    Article  Google Scholar 

  40. Adamczyk A, Niemiec J, Ambicka A, Małecki K, Wysocki WH, Mitus J, Rys J (2012) Expression of ER/PR/HER2, basal markers and adhesion molecules in primary breast cancer and in lymph nodes metastases: a comparative immunohistochemical analysis. Pol J Pathol 63(4):228–234

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank Dr. Saman Warnakulasuriya, Professor, Department of Oral Medicine, King’s College London, UK, for his valuable suggestions. The authors thank Dr. Puneet Gupta for performing the statistical analysis

Author information

Authors and Affiliations

  1. Department of Oral Pathology & Microbiology, Faculty of Dental Sciences, M.S. Ramaiah University of Applied Sciences, MSR Nagar, Bengaluru, 560054, Karnataka, India

    Wafa Khan, Vanishri C. Haragannavar, Roopa S. Rao, Samudrala Venkatesiah Sowmya & Dominic Augustine

  2. Department of Oral and Maxillofacial Surgery, Faculty of Dental Sciences, M.S. Ramaiah University of Applied Sciences, MSR Nagar, Bengaluru, 560054, Karnataka, India

    Kavitha Prasad

  3. Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan, Saudi Arabia

    Shankargouda Patil

Authors
  1. Wafa Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vanishri C. Haragannavar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roopa S. Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kavitha Prasad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Samudrala Venkatesiah Sowmya
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dominic Augustine
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shankargouda Patil
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shankargouda Patil.

Ethics declarations

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

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

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khan, W., Haragannavar, V.C., Rao, R.S. et al. P-Cadherin and WNT5A expression in assessment of lymph node metastasis in oral squamous cell carcinoma. Clin Oral Invest 26, 259–273 (2022). https://doi.org/10.1007/s00784-021-03996-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-021-03996-4

Keywords

Search

Navigation