Immunohistochemical Study of Fas/Fas-ligand and Cadherin Expression in Basal Cell Carcinoma in Sun-Exposed and Sun-Protected Areas

Kim, Ji Hyun; Suh, Ho Seok; Choi, Yu Sung

Abstract

BACKGROUND
UV radiation is the most important risk factor in the development of basal cell carcinoma (BCC). However, the association between tumorigenesis and the progression of BCC and UV exposure is complex, and the exact mechanisms remain to be elucidated.
OBJECTIVE
We tested the hypothesis that UV radiation affects BCC progression by triggering the tumor cells to escape from immune surveillance and by altering the cell-to-cell adhesion molecules.
METHODS
A retrospective study was conducted on 33 tissue samples of BCCs that underwent surgical resection between January 2010 to June 2018. We reviewed patient characteristics and evaluated Fas, Fas-ligand, CD8, PD-L1, E-cadherin, and P-cadherin expression in the tumor and peritumoral region by immmunohistochemical (IHC) staining.
RESULTS
BCCs in sun-exposed areas tended to have a shorter disease duration, but more patients reported an increase in size. Tumors in sun-exposed areas showed significantly lower Fas expression (p=0.005) and significantly higher Fas-ligand expression (p=0.022) compared to those in sun-protected areas. Peritumoral CD8 expression of tumor infiltrating lymphocytes (TILs) was less prominent in sun-exposed areas (p=0.011). E-cadherin expression was reduced in sun-exposed areas compared with that in sun-protected areas (p=0.006). Meanwhile, P-cadherin expression was preserved in most of the tumors in both the sun-exposed (95.2%) and sun-protected areas (100%).
CONCLUSION
This study showed that in BCCs, UV exposure induces Fas downregulation in the tumor, which helps the tumor to evade host immunity. Furthermore, UV exposure induces Fas-L upregulation in the tumor, which results in the apoptosis of CD8+ tumor-infiltrating lymphocytes. In addition, reduced expression of E-cadherin in sun-exposed areas indicates that UV exposure in BCCs leads to altered cell-to-cell adhesion, which allows further tumor motility.