Abstract
Purpose :
Cell-cell adhesion and cell-polarity protein complexes coordinate crucial processes that ensure epithelial integrity. Among these, the cell-cell adhesion molecule E-cadherin and the polarity protein PAR3 serve import functions in epithelial tissues and its loss is associated with dermal melanoma progression and elevated metastasis. The role of PAR3 or E-cadherin in conjunctival melanoma (CM) and in conjunctival squamous cell carcinoma (SCC) remains open. This study aims to analyze the expression of these central markers for cell-cell adhesion and cyto-architecture to gain insight into molecular changes during ocular surface tumor progression.
Methods :
The expression of epithelial PAR3 and E-cadherin in 32 patients with human SCC, CM and the corresponding precancerous lesions have been analyzed immunohistochemically in formalin-fixed paraffin-embedded tissues.
Results :
In SCC and its precancerous lesions conjunctival intraepithelial neoplasia (CIN) I-III, E-cadherin expression was significantly decreased compared to controls. Melanocytes and keratinocytes in healthy conjunctiva were E-cadherin positive. In CM E-cadherin expression was reduced. Conjunctival carcinomas switch their E-cadherin expression from extra- to intracellular. PAR3 was statistically significant decreased expressed in the epithelium of CIN I-III, SCC, CM, and the melanoma in situ probes compared to controls.
Conclusions :
In CIN, SCC, and CM a reduction of the cell-cell adhesion molecule E-cadherin and the polarity protein PAR3 is seen. This indicates that during carcinogenesis even the premalignant lesions lose expression of these markers. Loss of PAR3 and extracellular E-cadherin expression might be used as additional diagnostic tools to separate premalignant from benign lesions in the future and as a potential therapeutic target.
This is a 2021 ARVO Annual Meeting abstract.