Clinicopathological significance of primitive phenotypes in early gastric cancer with differentiated histology

Certain gastric cancers exhibit some primitive phenotypes, which may indicate a high malignancy. In histologically differentiated early gastric cancer (EGC), the presence and the clinicopathological significance of the primitive phenotype remain unclear. Using immunohistochemical staining we detected the expression of three primitive phenotypic markers SALL4, Glypican-3(GPC3), and AFP in whole tissue sections of differentiated EGC (gastrectomy specimens, n = 302). For those cases with primitive phenotypes, we analyzed their clinicopathological features and evaluated whether the criteria for endoscopic resection were met. We found that 9.3% (28/302) of all differentiated EGC cases have primitive phenotypes, and most of these cases (25/28) exhibit a histomorphology similar to conventional differentiated EGC. Patients with primitive phenotypes had a deeper invasion, a higher rate of ulcer and lymphatic invasion than cases without primitive phenotype. Moreover, patients with primitive phenotypes displayed a significantly higher frequency of LNM than those without (57.1% vs 8.8%, P