Expression Profiling as Biomarkers in Colorectal Serrated Carcinoma

Serrated adenocarcinoma (SC) is a recently recognized colorectal cancer (CRC) subtype, accounting for 7.2–9.2 % of CRC. SC has a worse prognosis than conventional carcinoma (CC) probably due to specific features at the invasive front including high-grade tumor budding and cytoplasmic pseudofragments, infiltrating growth pattern, and a weak peritumoral lymphocyte response. SCs also have a different profile of mutations in KRAS or BRAF oncogenes, expression of DNA repair proteins, and MSI status. Histological and immunohistochemical protein expression criteria have been proposed for SC diagnosis. Molecular profile studies have revealed that in agreement with previous observations, SCs have several cellular functions differentially regulated, such as hypoxia-, cytoskeleton-, vesicle transport-, and apoptosis-related pathways, among others. Expressions of several genes that participate in these pathways, like ephrin receptor B2, hippocalcin, and fascin1, have been proposed as biomarkers for differential SC diagnosis. miRNA expression and methylome signatures seem to corroborate these functions. All these findings suggest that the correct SC diagnosis may have important clinical implications and that the identified pathways and molecular targets could be exploited in the interest of SC specific patient follow-up and treatment. List of Abbreviations and Genes Abbreviations CC Conventional Carcinoma CIMP CpG island Methylation Phenotype CRC Colorectal Carcinoma CyPs Cytoplasmic Pseudofragments EMT Epithelial-Mesenchymal Transition HH Hedgehog Signaling Pathway IHC Immunohistochemistry LOH Loss of Heterozygosity miRNA MicroRNA MSI Microsatellite Instability MSI-H High Microsatellite Instability MSI-L Low Microsatellite Instability PLI Peritumoral Lymphocytic Infiltrate 632 M.C.T. Sevilla et al.