Understanding the Role of Fibroblast Growth Factor 8 (FGF8) in Tumors of the Ocular Adnexa.

Abstract

Purpose : Skin cancer is a common neoplasm with a high probability of 1 in 5 people developing it in their lifetime. One of the most common sites for non-melanoma skin cancer is the eyelid due to the constant exposure to stressors such as ultraviolet radiation, toxins, and infectious agents. Upper and lower eyelid tumors account for 60% of cancers of the ocular adnexa. A number of signalling pathways including FGF signalling have been shown to modulate progression of eyelid tumors. In this study, we have explored the role of FGF8 in the etiology and pathology of eyelid SGCs.

Methods : A human tissue array from normal and tumor eyelid tissues was developed using a standard protocol at Vancouver General Hospital. Hematoxylin and eosin (H&E) staining was performed on one replicate of the tissue array while the other replicate was probed for FGF8 expression and was blind scored by two pathologists. The statistical analysis on the score was carried out using GraphPad. A novel mouse model was created by overexpressing FGF8 in the skin following Keratin14-Cre-(K14Cre)-mediated recombination. Tissue samples from eyelids from mutant and wild-type littermates were fixed, embedded, and sectioned, followed by H&E staining.

Results : The human tissue array shows a 6.5-fold increase in the expression of FGF8 in tumors of the eyelid when compared to their normal tissue counterparts (n=3, p<0.0001, Student T-test). The FGF8-overexpressing transgenic mice developed eyelid tumors with 100% penetrance rate. In addition, 75% of the transgenic mice died ~6 months post–birth due to tumor load and metastasis. Histological analyses of paraffin sections using H&E showed an increase in the number of lipid-containing vacuoles. The autopsy of K14Cre; FGF8GOF mice revealed enlarged and altered morphology of cervical lymph nodes.

Conclusions : The generation of eyelid tumors in FGF8 transgenic mice strongly correlate with the increased expression of FGF8 in human eyelid tumor. Based on our preliminary findings, we hypothesize that FGF8 is critical for the etiology and pathology of eyelid SGCs.

This is a 2020 ARVO Annual Meeting abstract.

 

Figure 1 –K14Cre;Fgf8GOF and wild-type littermate at P14 (A) and P90 (B). Close-up view of right (C) and left (D) eye of K14Cre;Fgf8GOF showing presence of lesions.