Abstract
Vulvar squamous cell carcinoma associated with lichen sclerosus (VLS-VSCC) are rare tumors but with higher recurrence and worse prognosis than other types of VSCC. Lack of experimental models has limited the search for better understanding of the biology and development of treatment modalities. In this study, we isolated and characterized primary cells from VSCC (n = 7) and normal vulvar tissue adjacent to tumor (n = 7). Detailed characterization of the novel spontaneously immortalized cell line, VCC1 revealed a characteristic epithelial morphology in vitro and a well-differentiated keratinizing SCC histology in vivo, closely resembling the tumor of origin. VCC1 expressed higher levels of epithelial-mesenchymal transition markers and higher clonogenic properties as compared to other established non VLS-VSCC cell lines. In vitro 3D organotypic assays and in vivo xenografts revealed a prominent role of cancer-associated fibroblasts in VCC1 invasion and tumor formation. In conclusion, VCC1 mirrored several major VLS-VSCC features and provided a robust experimental tool for further elucidation of VLS-related oncogenesis and drug testing.
Highlights
With an incidence of 0.5–1.5 in 100,000 individuals per year, carcinoma of the vulva represents about 4% of all female genital cancers [1]
VCAF1 were negative for cytokeratin 10 (CK10) and positive for vimentin (Fig. 1B c, d)
Infrequent incidence of vulva squamous cell carcinoma associated with lichen sclerosus et atrophicus compared to other female genital cancers coupled with advanced age of patients has hampered genetic and molecular studies on vulvar lichen sclerosus (VLS)-related tumorigenic pathways [23,24]
Summary
With an incidence of 0.5–1.5 in 100,000 individuals per year, carcinoma of the vulva represents about 4% of all female genital cancers [1]. According to the latest and widely accepted grading system, the previously used VIN terminology has been replaced by cytology-based squamous intraepithelial lesions (SIL) terminology [5,6]. These precancerous lesions are divided into three types: low-grade squamous intraepithelial lesions (LSIL, VIN1); high-grade intraepithelial lesions (HSIL, VIN 2,3 or usual VIN) and a very differentiated variant, called dVIN. Such grading systems correlates with the risk to cancer progression over time [6]
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