Abstract 2987: Comparison of the anticancer effects of Mitomycin-C and 5-Fluorouracil on novel periocular sebaceous carcinoma cell lines

Abstract

Abstract Background: Sebaceous carcinoma (SC) is a highly malignant and potentially lethal neoplasm that most commonly arises from the ocular adnexa. Surgical management is the current mainstay of treatment; however, globe sparing tumor control is often complicated by pagetoid (or intraepithelial) invasion. Topical mitomycin-c (MMC) or 5-fluorouracil (5-FU) have been used as adjunctive medical therapy on the basis of their success in treating other ocular neoplasms. Yet, little is known of their effects on SC tumorgenicity. Here, we characterized effects of MMC and 5-FU in SC in vitro. Methods: Periocular SC tissue samples were collected from two patients with histologically confirmed disease. This study was approved by the University of Miami Institutional Review Board and was conducted in a Health Insurance Portability and Accountability Act of 1996—compliant manner. Molecular characterization of the SC cells was done by immunocytochemistry and whole exome sequencing. SC cells were treated with MMC and 5-FU. The cytotoxic effects were evaluated using a viability assay and the kinetics of these effects were investigated by measuring cell proliferation over time. Migration capability of SC cells after drug treatment was examined by wound healing assays. Results: Two SC cell lines, called Bascom Palmer 50 and 52 (BP50 and BP52), were established. Both cell lines retain the immunophenotypic and molecular features of SC. MMC reduced cell viability in both cell lines in a dose-dependent manner. MMC decreased SC cell proliferation and reduced overall cell number significantly compared to the untreated controls in a dose-dependent manner. MMC also inhibited SC migration capacity significantly. Conversely, 5-FU treatment did not affect cell viability or migration capacity in a dose-dependent fashion. While treatment with high-dose 5-FU inhibited SC proliferation, it did not reduce cell number below baseline. Conclusions: We successfully generated SC cell lines and characterized the effects of MMC and 5-FU on these lines. Clinical medical management of periocular SC has been based of empirical data. Our findings suggest that MMC possess superior cytotoxic and cytostatic activity against SC compared to 5-FU in vitro. Taken together, these preliminary findings indicate that MMC may be more efficacious than 5-FU in the treatment of periocular SC. Currently, investigations are underway to identify novel therapeutic targets and test their efficacy in our cell lines. Citation Format: Steven H. Lang, Ryan A. Gallo, Michelle G. Zhang, David T. Tse, Daniel Pelaez, Andrew J. Rong. Comparison of the anticancer effects of Mitomycin-C and 5-Fluorouracil on novel periocular sebaceous carcinoma cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2987.