Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul-Sep;27(3):507-514.
doi: 10.4103/jomfp.jomfp_28_23. Epub 2023 Sep 12.

Differential expression of Cadherins switch and Caveolin-2 during stages of oral carcinogenesis

Rebeca B Nascimento  1 , Isadora A R Machado  1 , Jamerson C Silva  2 , Lorena A S Faria  3 , Fernanda C Borba  3 , Lia P A Porto  4 , Jean N Santos  5 , Luciana M P Ramalho  5 , Camila O Rodini  6 , Maria Fernanda S D Rodrigues  7 , Katiúcia B S Paiva  8 , Flávia C A Xavier  5
Affiliations

Differential expression of Cadherins switch and Caveolin-2 during stages of oral carcinogenesis

Rebeca B Nascimento et al. J Oral Maxillofac Pathol. 2023 Jul-Sep.

Abstract

Background: Oral squamous cell carcinoma (OSCC) accounts for 90% of oral malignancies, which may be preceded by oral potentially malignant disorders (OPMDs). Cancer progression involves the downregulation of epithelial markers (E-cadherin) and the upregulation of mesenchymal markers (N-cadherin), which together characterise the epithelial-mesenchymal transition (EMT). Furthermore, caveolin can act on cell adhesion and migration events that regulate the expression of the E-cadherin/α-β-catenin complex, thus favouring aggressive biological behaviour. This study aimed to analyse the immunoexpression of E-cadherin, N-cadherin and caveolin-2 at different stages of oral carcinogenesis to identify reliable biomarkers to predict malignant potential.

Methods: Expressions of E-cadherin and N-cadherin in 14 normal oral mucosae (NOM), 14 OPMD and 33 OSCC specimens were evaluated using immunohistochemistry. Clinicopathological parameters were also assessed.

Results: E-cadherin immunoexpression was significantly reduced during the progression of oral carcinogenesis (P = 0.0018). N-cadherin immunoexpression did not show any statistical differences between these groups. However, a representative number of N-cadherin-positive OSCC cases did not express E-cadherin. The expression of caveolin-2 increased significantly with the progression of the disease, from NOM to OSCC (P value: 0.0028).

Conclusion: These findings indicate that cadherin switch and caveolin-2 immunoexpression may be regulatory events in oral carcinogenesis.

Keywords: Cadherins; caveolin-2; immunohistochemistry; oral squamous cell carcinoma.

PubMed Disclaimer

Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
Immunoexpression of E-cadherin, N-cadherin and caveolin-2 during stages of oral carcinogenesis. E-cadherin shows intense membranous immunoexpression in normal oral mucosa (NOM) in almost all layers (a), weak cytoplasmic immunoexpression in oral potentially malignant disorder (OPMD) in basal/suprabasal layer (b) and moderate membranous/cytoplasmic immunoexpression distributed in an irregular pattern of oral squamous cell carcinoma (OSCC) tumoral islands (c). N-cadherin shows intense nuclear immunostaining in NOM (d), moderate membranous immunoexpression in OPMD (e) and moderate membranous/cytoplasmic immunoexpression in OSCC tumoral island (f). Caveolin-2 shows intense membranous/cytoplasmic immunoexpression in the basal/suprabasal layer of NOM (g), predominantly in the basal layer of OPMD (h) in an irregular pattern and intense membranous/cytoplasmic immunoexpression in the invasive island of OSCC (i). The scales indicate 100 μm (a, c and d) and 50 μm (b, e, f, g, h and i)
Figure 2
Figure 2
Cadherins and caveolin-2 differential immunoexpression in cell compartment during oral carcinogenesis. (a) During the cancer progression model, the epithelial–mesenchymal transition signalling promotes cancer cell invasion. Preserved E-cadherin expression (membrane) in the suprabasal layer in normal oral mucosa (NOM) is followed by abnormal (membranous/cytoplasmic) expression in oral potentially malignant disorder (OPMD) and oral squamous cell carcinoma (OSCC). Otherwise, the N-cadherin cytoplasmic/nuclear staining pattern in the basal/suprabasal layer of NOM is followed by membranous/cytoplasmic pattern in OPMD and cytoplasmic/nuclear in OSCC. Membranous CAV-2 immunoexpression pattern in NON and OPMD is followed by membranous/cytoplasmic pattern, through a gain of expression. (b) In poorly differentiated tumours, we observe membrane N-cadherin and CAV-2 and cytoplasmic CAV-2 expression
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide:Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86. - PubMed
    1. Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45:309–16. - PubMed
    1. Sloan P, Gale N, Hunter K, Lingen MW, Nylander K, Reibel J, et al. Malignant surface epithelial tumours. In: El-Naggar AK, Chan JK, Grandis Jennifer R, Takata T, Slootweg PJ, editors. WHO Classification of Head and Neck Tumours. 4th ed. Lyon: WHO; 2017. pp. 109–11.
    1. Kujan O, Oliver RJ, Khattab A, Roberts SA, Thakker N, Sloan P. Evaluation of a new binary system of grading oral epithelial dysplasia for prediction of malignant transformation. Oral Oncol. 2006;42:987–93. - PubMed
    1. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2:442–54. - PubMed