Rapid, quantitative prediction of tumor invasiveness in non-melanoma skin cancers using mechanobiology-based assay

Abstract

Non-melanoma skin cancers, including basal and squamous cell carcinomas (BCC and SCC), are the most common malignancies worldwide. BCC/SCC cancers are generally highly localized and can be surgically excised; however, invasive tumors may be fatal. Current diagnosis of skin cancer and prognosis of potential invasiveness are based mainly on clinical-pathological factors of the biopsied lesions. SCC invasiveness is also predicted by histomorphological factors, such as the degree of differentiation or the mitotic index, while BCCs are typically considered non-invasive. The above subjective measures do not provide direct, objective prognosis of cellular invasiveness in each specific sample. Hence, we have developed a mechanobiology-based approach to rapidly determine sample invasiveness. Here, cells from 15 fresh tissue samples of suspected non-melanoma skin cancer were seeded on physiological-stiffness (2.4 kPa) synthetic gels, and within 1-h invasive cell subsets were observed to push/indent the gel surface; clinicopathological results were separately obtained using standard protocols. The percentage of indenting cells from invasive (26.2 ± 2.4%) and non-invasive (4.8 ± 0.5%) SCC samples differed significantly (p < 0.0001), with well-separated invasiveness cutoffs of, respectively, > 12% and < 5%. The mechanical invasiveness directly agrees with the SCC cell-differentiation state, where over 3.3-fold more (p < 0.0001) cells from moderately differentiated samples indent the gels as compared to well-differentiated cell samples. In BCCs, < 20% of cells typically indented, and a highly migratory, desmoplastic sample was identified with 46%. By providing rapid, quantitative, early prognosis of invasiveness and potential metastatic risk, our rapid technology may facilitate informed (bed-side) decision making and choice of disease-management protocols on the time-scale of the initial diagnosis and surgical excision.

Keywords: Cancer invasion; Early prognosis; Mechanobiology; Metastatic potential; Non-melanoma skin cancer.