sdj-10030

Immunohistochemical expression of P-cadherin and cortactin in oral squamous cell carcinomas

*Dena N. Mohammad, *Balkees T. Garib, **Hassanain H. Khudeir & *Ban A Abdul–Majeed

*College of Dentistry, University of Sulaimani

**College of Medicine, University of Baghdad

DOI: https://doi.org/10.17656/sdj.10030

Abstract

Objectives: to assess the expression and pattern distribution of P-cadherin and cortactin in OSCC, and to relate such expression to the histopathological grading.

Materials and Methods: An immunohistochemical staining for P-cadherin and cortactin was performed on paraffin blocks of 40 oral squamous cell carcinoma and five normal mucosa. Fisher's exact test and Spearman's rank-order correlation were applied for analysis. P < 0.05 was considered statistically significant.

Results: P-cadherin was either aberrantly cytoplasmic re-localized or lost in 45% of cases. 58.6% of positive cases were in grade I. Focal heterogeneous pattern was the commonest pattern (27.5%) and related to the degree of cell differentiation. The expression percentage was reported mainly in score 1 and 2 with no differences among histopathological grades (P=0.778). On the other hand, 70% of oral SCC had cytoplasmic cortactin expression. The majority of cases (85.7%) expressed diffuse pattern including all positive grade II and III cases. Nevertheless, statistical analysis did not reach a significant level (P= 0.722). Furthermore, no significant correlation was found between P-cadherin and cortactin expression.

Conclusion: Oral SCC had P-cadherin under-expression (focal) and cortactin over-expression (diffuse). The P-cadherin pattern distribution rather than expression percentage was related to the degree of cell differentiation. The expressions of these molecules were unrelated to each other.

Keywords: oral squamous cell carcinoma, P-cadherin, cortactin.

Full Article - PDF

References:

1.       Soames JV aand Southam JC,  Oral Pathology: Oral epithelial tumors, melanocytic naevi, and malignant melanoma. 3rd ed, Oxford; Oxford Univ Press. 1998: 161. 

2.       Me ́ ndez E, Cheng C, Farwell DG, Ricks S, Agoff SN,

Futran ND, Weymuller EA, Maronian NC, Zhao LP and Chen C, 2002. Transcriptional expression profiles of oral squamous cell carcinomas. Cancer. 2002; 95(7): 1482-94.

3.       Humayun S and  Prasad VR. Expression of p53 protein and Ki-67 antigen in oral premalignant lesions and oral squamous cell carcinomas: An immunohistochemical study. Natl J Maxillofac Surg. 2011; 2(1):38-46.

4.       Parades J. CDH3/P-cadherin overexpression in breast carcinomas: its regulatory mechanisms, the role in cell invasion, and the association with cancer stem cell properties. BMC Proc. 2010;4 (Suppl 2):017.

5.       O’Donnell RK, Feldman M, Mick R and Muschel RJ. Immunohistochemical method identifies lymph vascular invasion in a majority of oral squamous cell carcinomas and discriminates between blood and lymphatic vessel invasion. J Histochem Cytochem. 2008; 56 (9): 803-10.

6.       Choi S and Meyers JN. Molecular pathogenesis of oral squamous cell carcinoma: implications for therapy. J Dent Res. 2008; 87(1):14-32.

7.       Thiery JP and Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 2006; 7(2):131-42.

8.       Lo Muzio L, Campisi G, Farina A, Rubini C, Pannone G, Serpico R, Laino G, De Lillo A and Carinci F. Pcadherin expression and survival rate in oral squamous cell carcinoma: an immunohistochemical study. BMC Cancer. 2005; 21(5):63.

9.       Lo Muzio L, Pannone G, Mignogna MD, Staibano S, Mariggi  MA, Rubini C, Procaccini M, Dolci M, Bufo P, De Rosa G and  Piattelli  A. P-cadherin  expression predicts  clinical  outcome  in  oral  squamous  cell carcinomas.  Histol Histopathol. 2004; 19(4):1089-99.

10.     Munoz-Guerra MF, Marazuela EG, FernándezContreras ME and Gamallo C. P-cadherin expression reduced in squamous cell carcinoma of the oral cavity: an indicator of poor prognosis. Cancer. 2005; 103(5): 960-9.

11.     Bauer R, Dowejko A,  Driemel  O,  Boßerhoff  AK and Reichert  TE.  Truncated P-cadherin is  produced  in oral  squamous  cell carcinoma.  FEBS J. 2008; 275(16):4198-210.

12.     Yamada SI, Yamamoto S, Kawasaki G, Mizuno A and Nemoto TK. Overexpression of cortactin increases invasion potential in oral squamous cell carcinoma. Pathol Oncol Res. 2010; 16(4):523-31.

13.     Paredes  J, Albergaria A, Oliveira JT, Jerónimo C, Milanezil F and Schmitt FC. P cadherin overexpression is an indicator of clinical outcome in invasive breast carcinomas and is associated with CDH3 promoter hypomethylation.  Clin Cancer Res. 2005 Aug 15; 11(16):5869-77.

14.     Greer RO Jr, Said S, Shroyer KR, Marileila VG and Weed SA. Overexpression of cyclin D1 and cortactin is primarily independent of gene amplification in salivary gland adenoid cystic carcinoma. Oral Oncol. 2007; 43(8):735-41.

15.     Hideki  K,  Masahiro  W and Akio  T,  Expression  of  Pcadherin  and  cyclin  D1  in  oral  squamous  cell carcinoma.  J  Osaka Odontological Society. 2002; 65:1-10. 

16.     Hirakawa H, Shibata K and Nakayama T. Localization of cortactin is associated with colorectal cancer development. Int J Oncol. 2009; 35(6):1271-6.

17.     Williams HK, Sanders DS, Jankowski JA, Landini G and Brown AM. Expression of cadherins and catenins in oral epithelial dysplasia and squamous cell carcinoma. J Oral Pathol Med. 1998; 27(7):308-17.

18.     Pyo SW, Hashimoto M, Kim YS, Kim CH, Lee SH, Johnson KR, Wheelock MJ and Park JU. Expression of E-cadherin, P-cadherin and N-cadherin in oral squamous cell carcinoma: correlation with the clinicopathologic features and patient outcome. J Craniomaxillofac Surg. 2007; 35(1):1-9.

19.     Schmalhofer O, Brabletz S and Brabletz T. E-cadherin, beta-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev. 2009; 28(1-2):151-66.

20.     Taniuchi K, Nakagawa H, Hosokawa M, Nakamura T,

Eguchi H, Ohigashi H, Ishikawa O, Katagiri T and Nakamura Y. Overexpressed P-cadherin/CDH3 promotes motility of pancreatic cancer cells by interacting with p120ctn and activating rho-family GTPases. Cancer Res. 2005; 65(8):3092-9.

21.     Hofman P, Butori C, Havet K, Hofman V, Selva E, Guevara N, Santini J and Obberghen-Schilling EV. Prognostic significance of cortactin levels in head and neck squamous cell carcinoma: comparison with epidermal growth-factor receptor status. Br J Cancer. 2008; 98: 956–64.  

22.     Rothschild BL, Shim AH, Ammer AG, Kelley LC, Irby

KB, Head JA, Chen L, Varella-Garcia M, Sacks PG, Frederick B, Raben D and Weed SA. Cortactin overexpression regulates actin-related protein 2/3 complex activities, motility, and invasion in carcinomas with chromosome 11q13 amplification. Cancer Res. 2006; 66: 8017–8025.  

23.     Rodrigo JP, García LA, Ramos S, Lazo PS and Suárez C. EMS1 gene amplification correlates with poor prognosis in squamous cell carcinomas of the head and neck. Clin Cancer Res. 2000; 6(8):3177-82.

24.     Tsai WC, Jin JS, Chang WK, Chan DC, Yeh MK, Cherng SC, Lin LF, Sheu LF and Chao YC. Association of cortactin and fascin-1 expression in gastric adenocarcinoma: correlation with clinicopathological parameters. J Histochem Cytochem. 2007; 55(9): 955-62.

 © The Authors, published by University of Sulaimani, College of Dentistry

This work is licensed under a Creative Commons Attribution 4.0 International License.