Clinicopathological Characteristics and Genetic Alterations of Mixed-type Early Gastric Carcinomas

Mixed-type gastric carcinomas show a progressive loss of glandular structure and a histological transformation from differentiated-type to undifferentiated-type carcinoma during the progression of the tumor. In this study, we determined the clinicopathological characteristics and genetic alterations of mixed-type early gastric carcinomas. The clinicopathological findings in 68 cases of early gastric carcinoma classified as mixed-type carcinoma (MTC) were examined and compared with 88 cases of differentiated-type carcinoma (DTC) and 50 cases of undifferentiated-type carcinoma (UTC). The expression of the phenotypic markers for human gastric mucin, mucin 6, mucin 2 and CD10 were examined. Furthermore, the presence of mutations in APC and TP53 and the microsatellite instability status of the tumor were also determined. MTCs had significantly increased depth of invasion, lymphatic vessel invasion, and lymph node metastases, compared to DTCs. UTCs also had significantly more lymph node metastases compared to DTCs. Both MTCs and UTCs had a higher incidence of human gastric mucin expression and a lower incidence of CD10 expression, compared to DTCs, (85.3% and 92.0% vs. 52.3%, P < 0.001 and P < 0.001; 13.2% and 6.0% vs. 30.7%, P = 0.01 and P < 0.001, respectively). MTCs showed a higher frequency of TP53 mutation compared to DTCs (42.6% vs. 27.3%, P = 0.04). This study shows that MTCs as well as UTCs are more aggressive tumors than DTCs. The differences in biological behavior among these groups may result from their different genetic backgrounds during the early stage of gastric carcinogenesis.