Differential molecular expression patterns associated with metastasis in cutaneous squamous cell carcinoma: A systematic review and meta-analysis.

Abstract The majority of cutaneous squamous cell carcinomas (CSCC) are cured with surgical removal, however, approximately 4% of tumors will metastasize. Molecular expression testing may improve accuracy in estimating prognosis and defining mechanisms important in disease progression that may impact response to therapy. Using PubMed/MEDLINE and EMBASE, a systematic review was performed to evaluate studies published from January 2005 to August 2019 reporting tumor protein or RNA expression along with either outcomes (metastasis or death) or comparison of primary versus metastatic tumor samples. Inclusion criteria were met by 45 studies containing 81 comparisons of 44 distinct proteins and 25 miRNAs. On meta-analysis of studies analyzing primary tumor samples in terms of later outcomes, high primary tumor expression of PD-L1 (OR 2.34, 95% CI 1.09-5.02, p=0.030), EGFR (OR 2.57, 95% CI 1.24-5.33, p=0.011) and podoplanin (OR 2.33, 95% CI 1.00-5.41, p=0.049) conferred increased odds for metastasis. In comparisons of primary to metastatic tissue, metastatic tissue was more likely to have high expression of PD-L1 (OR 3.13, 95% CI 1.00-9.75, p=0.049). Further studies are needed to confirm if testing for PD-L1, EGFR, and podoplanin expression aids in CSCC prognostic estimation of metastasis or death, or predicts response to therapy.