BACKGROUND: Cutaneous Squamous Cell Carcinoma (cSCC) is one of the most common types of non-melanoma skin cancer. Histopathologic variants of cSCC show significantly different clinical behavior and their correct classification is critical for diagnosis, prognosis and therapy.

METHOD: In the present study, we employed laser-capture microdissection coupled with liquid chromatography–tandem mass spectrometry (LC-MS) to test the feasibility of using archival formalin-fixed paraffin embedded (FFPE) cSCC material (five patients) for proteomic investigations that could provide reliable biomarkers for the cSCC clinical management. Pair-wise comparisons were performed between proteomes extracted from tumor and adjacent morphologically normal tissue for each patient. Ingenuity Pathway Analysis (IPA) bioinformatics suite was used to interpret the roles of altered proteins in cSCC pathophysiology. Oncomine database was used to assess the gene expression levels of proteins changed in our dataset.

RESULT AND DISCUSSION: In total, 1310 unique protein species were identified across all five patients. Of these, an average of 144 proteins were significantly increased and 88 proteins decreased in the tumor samples compared to their normal counterparts (p<0.05). IPA analysis revealed the disruptions are mainly in proteins and upstream regulators associated with the regulation and control of cell proliferation, apoptosis, and cell movement.  Genes corresponding to 18 proteins were also differentially expressed at the transcript level in silico, supporting our initial proteomic measurements.

CONCLUSION: Our findings confirmed that label-free mass spectrometry-based quantitative proteomics is a useful platform for analyzing FFPE cSCC tissues.