Squamous cell carcinoma (SCC) is the second most common form of skin cancer. In most cases, SCC is highly curable with surgical excision alone. However, a small subset of SCC tumors, approximately 5%, will go on to metastasize and spread despite complete surgical removal. Identifying which SCC tumors are high-risk has been challenging.
Current tumor staging systems, which classify SCCs based on clinical and pathological features, have had limited success predicting which tumors are likely to metastasize. Even the most advanced staging system developed to date only identifies a group of SCCs with a 25% risk of spreading to lymph nodes and a 20% risk of causing death. This risk level is not high enough to recommend additional treatment beyond surgery.
To address this issue, my research group performed a gene expression analysis on 230 patients with primary cutaneous SCC. By examining mRNA levels, we identified 18 genes that are differentially expressed between SCC tumors that later recurred versus those that were cured by surgery alone. Using these 18 genes, we developed a predictive model that can classify SCC tumors as high or low risk for metastasis and recurrence.
Promisingly, our gene expression test demonstrated 70% sensitivity and 90% specificity for predicting SCC tumors that later recurred. Most importantly, it had a positive predictive value of 50% – identifying a group of SCCs with a 50% risk of metastasis. This is double the predictive ability of the best tumor staging system currently available.
Patients with SCC tumors classified as high-risk by this 18-gene test would be clear candidates for additional therapy beyond surgery, such as adjuvant radiation or drug treatment. The test could also be used to identify high-risk patients eligible for clinical trials of new adjuvant therapies for SCC.
In summary, by examining gene expression patterns, we have developed a novel test that can predict SCC tumors with a high risk of metastasis and recurrence more accurately than any previous method. This test has the potential to usher in a new era of precision medicine for squamous cell skin cancer, allowing us to identify and treat the most dangerous tumors early. We are excited to further validate and refine this promising new diagnostic tool.