Abstract
BackgroundCertain 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.MethodsUsing 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.ResultsWe 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 < 0.001). Multivariate analysis revealed that presence of primitive phenotypes was an independent risk factor for LNM (P = 0.001, HR 6.977, 95% CI: 2.199–22.138). Interestingly, we found 2 cases with primitive phenotypes developed LNM, and they both met the expanded indications of endoscopic resection for differentiated EGC.ConclusionsA small number of differentiated EGC have primitive phenotypes, which were closely related to LNM and were an independent risk factor for LNM. Given its highly aggressive behavior, differentiated EGC with primitive phenotypes should be evaluated with stricter criteria before endoscopic resection, or considered to give an additional surgical operation after endoscopic resection.
Highlights
Gastric cancer (EGC) refers to gastric cancer that does not invade deeper than the submucosa, regardless of lymph node metastasis (LNM)
Detection of the primitive phenotype in differentiated early gastric cancer (EGC) Immunohistochemistry in whole tissue sections reveal that among 302 cases of differentiated EGC: 1) 24 cases were SALL4 positive, of which 13 were diffusely positive and 11 were focally positive; 2) 8 and 2 were positive for GPC3 and AFP respectively, and both GPC3 and AFP were focally positive (Fig. 1). 3) 274 cases were negative for SALL4, GPC3, and AFP
The expression of AFP was associated with diffuse expression of SALL4 (P < 0.001, Kappa value 0.258), and there existed an association between AFP expression and GPC3 expression (P < 0.001, Kappa value 0.214)
Summary
Gastric cancer (EGC) refers to gastric cancer that does not invade deeper than the submucosa, regardless of lymph node metastasis (LNM). Endoscopic resection of EGC is applied based on the premise that the patients do not have LNM, and it is vital to assess the risks of LNM for EGC. Indications for endoscopic resection have been established, and these indications can evaluate LNM risks of EGC. Several clinicopathological variables, such as tumor size, depth of invasion, ulcer presence, lymphatic/vascular invasion and tumor differentiation are included in these indications. Differentiated EGC has a lower incidence of LNM than undifferentiated EGC, it is still important to evaluate LNM risks for differentiated EGC. 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
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