Signet-ring-cell carcinoma (SRCC) is a rare variant of adenocarcinoma, accounting for about 10% of gastric cancer (GC) and 1% of colorectal cancer
(CRC). Despite a decrease in the overall incidence of GC in recent decades, the incidence of SRCC is constantly increasing, in Asia, United States and Europe .
Generally, SRCC is associated with female gender and young age of onset compared to non-SRCC . In advanced GC, SRCCs is also associated with poor differentiation, diffuse type, distal location. More importantly, SRCCs display worse prognosis than non-SRCC counterparts .
Accordingly, CRC-SRCC has been shown to be associated with advanced tumor stage at presentation and worse outcomes . Recently, it has been observed that 50% or less of signet-ring cell component is associated with higher mortality, independent of other clinicopathologic and molecular features (microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutations) .
However, the molecular characteristics underlying the biology of these tumors have not been elucidated yet .
Herein, we aimed to comprehensively characterize the molecular features of SRCCs. Furthermore, we compared SRCCs tumors arising GC vs CRC to evaluate whether SRCC histology harbor molecular similarities, regardless of tumor location. Finally, we investigated whether SRCCs harbor different molecular characteristic compared with non-SRCC counterparts.
Our research is the first to comprehensively characterize the molecular features of SRCC from gastric and colorectal tumors. Our data suggest that SRCCs harbor similar molecular profile, regardless the tumor location. On the other hand, significant differences were observed between SRCCs and non-SRCC both within GC and CRC. Therefore, histology-driven tailored therapy should be provided to these patients. Further studies are warranted to elucidate molecular mechanisms accounting for the aggressive behavior of SRCCs.Download Publication