Metastatic Cutaneous Squamous Cell Carcinoma: Differential Gene Expression Profiling in Comparison to Primary Cutaneous Squamous Cell Carcinoma
Albert Su, Seong Ra, Xinmin Li, Scott Binder. UCLA Medical Center, Los Angeles, CA; San Diego Pathologists Medical Group, San Diego, CA
Background: Squamous cell carcinoma (SCC) is the second most common cutaneous malignancy with a substantial minority that metastasize. Regional or distant spread is associated with a poor outcome. Lesions that are likely to metastasize require prompt treatment. The molecular mechanisms involved in the progression to metastasis are incompletely understood. Our goal was to utilize comprehensive DNA microarrays to investigate the molecular pathways involved in the progression of cutaneous SCC to metastasis.
Design: DNA microarray studies with the AffymetrixU133plus2.0 array were performed on formalin-fixed and paraffin-embedded blocks of skin: 10 cases of primary cutaneous SCC and 10 cases of metastatic cutaneous SCC to lymph nodes, salivary glands, and soft tissue. The data were analyzed using Partek Genomics Suite and Ingenuity Pathway Analysis software.
Results: Metastatic cutaneous SCC had 106 differentially expressed genes in comparison with primary cutaneous SCC (>=2 fold change, FDR p<=0.01) with 92 genes upregulated and 14 genes downregulated. The most significantly upregulated genes included CDR1, TPM4, MALAT1, TMED2, and FN1. The most significantly downregulated genes included FLG2, LOR, HAL, TYRP1, and FLG. Canonical pathway analysis showed that many cancer related pathways that lead to cell migration and invasion, including PI3K/AKT signaling, are activated in metastatic cutaneous SCC.
Conclusions: There are clear patterns of differential gene expression between primary cutaneous SCC and metastatic cutaneous SCC. These differentially expressed genes and enriched pathways further our understanding of the molecular events involved in the progression of cutaneous SCC to metastasis and may suggest new targets for prognostication and therapy.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 66, Wednesday Morning