Cutaneous squamous cell carcinoma (cSCC) possesses metastatic potential and in metastatic case the prognosis is poor. At present, there are no established biomarkers for assessment of metastasis risk or prognosis of primary cSCC. Cancer-associated fibroblasts (CAFs) promote the progression of cancer, but there is limited evidence of their role in cSCC. Here, we have examined the potential of CAF markers in the assessment of metastasis risk and prognosis of cSCC. We used multiplexed fluorescence immunohistochemistry to profile CAF landscape in metastatic and non-metastatic primary human cSCCs, actual metastases, and in premalignant and benign epidermal lesions. Quantitative high-resolution image analysis was performed with two separate panels of antibodies for CAF markers and the results were correlated with clinical and histopathological parameters including disease-specific mortality. Increased stromal expression of fibroblast activation protein (FAP), α-smooth muscle actin (α-SMA), and secreted protein acidic and rich in cysteine (SPARC) was associated with progression of ultraviolet-induced premalignant lesions to invasive cSCC. Elevation of FAP and platelet-derived growth factor receptor-β (PDGFRβ) expression was associated with progression of primary cSCC to metastatic stage. High stromal expression of PDGFRβ and periostin correlated with poor prognosis. PDGFRα-/PDGFRβ+/FAP+ CAF subset was associated with invasion and metastasis and independently predicted poor cSCC-specific survival. Fibroblast activation evolves during the progression of cSCC. High PDGFRβ expression alone and PDGFRα-/PDGFRβ+/FAP+ CAF phenotype appear as biomarkers for the progression of primary cSCC to metastatic stage, and for poor prognosis.

ESDR466 - Cancer-associated fibroblast activation predicts progression, metastasis and prognosis of cutaneous squamous cell carcinoma

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.