Signet ring cell carcinoma

Signet ring cell carcinoma (SRCC) is a rare form of highly malignant adenocarcinoma that produces mucin. It is an epithelial malignancy characterized by the histologic appearance of signet ring cells.Gastric signet ring cell carcinoma. H&E stain. Signet ring cell carcinoma (SRCC) is a rare form of highly malignant adenocarcinoma that produces mucin. It is an epithelial malignancy characterized by the histologic appearance of signet ring cells. Primary SRCC tumors are most often found in the glandular cells of the stomach (SRCC originates in the stomach in 90 percent of patients), and less frequently in the breast, gallbladder, urinary bladder, and pancreas. SRCCs do not normally form in the lungs, though a few incidences have been reported. Among colorectal cancers, the prevalence of SRCC is less than one percent. Though incidence and mortality of gastric cancer has declined in many countries over the past 50 years, there has been an increase in occurrences of gastric SRCC-type cancers. SRCC tumors grow in characteristic sheets, which makes diagnosis using standard imaging techniques, like CT and PET scans, less effective. Some cases are inherited, and these cases are often caused by mutations in the CDH1 gene, which encodes the important cell–cell adhesion glycoprotein E-cadherin. A down-regulation of E-cadherin is essential for the initiation and progression a gastric signet ring cell cancer cells. Once those cells lose E-cadherin, their motility increases due to an epithelial-mesenchymal transition.Somatic mutations of the APC gene have also been implicated in the development of gastric SRCCs. The role of other risk factors in gastric cancer such as salt-preserved food, smoking, auto-immune gastritis are not well studied in SRCC. SRCCs are dedifferentiated adenocarcinomas that lose the capability for cell–cell interaction. Highly differentiated adenocarcinomas form SRCCs via a loss of adherens and tight junctions that typically separate MUC4, a mucin protein, and ErbB2, an oncogenic receptor. When MUC4 and ErbB2 are able to interact, they trigger an activation loop. As a result, the ErbB2/ErbB3 signaling pathway becomes constitutively activated, cell–cell interactions are lost and signet carcinomas are formed. Constitutive action of the ErbB2/ErbB3 complex also enhances cell growth. The mechanism of this malignant cancer is still unclear; however, it has been found that a colon carcinoma cell known as HCC2998 causes an increase in differentiated tumor production. The reason for this increase is due to active PI3K that are converted to a SRCC-like cells.