Prognostic Threshold of Neuroendocrine Differentiation in Gastric Carcinoma: a Clinicopathological Study of 945 Cases

PURPOSE: The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications. MATERIALS AND METHODS: Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED (PNED) and demographic and clinicopathological parameters. RESULTS: In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. PNED, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff PNED was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher PNED. Tumors with ≥10% NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED. CONCLUSIONS: GC with ≥10% NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.

Relationship of Mena expression and SNP polymorphisms with the susceptibility and prognosis of gastric cancer / 中国肿瘤临床

Objective:To investigate the correlation of Mena protein expression with the invasion and metastasis of Mena SNPs with genetic susceptibility in gastric cancers (GC). Methods:A tissue microarray that simulates the invasion and metastasis process of GC was created, and immunohistochemistry was performed to detect the expression of Mena protein. The Mena gene 5 SNP loci geno-types of 188 healthy people and 389 GC patients were assayed using PCR-based LDR analysis. Results:The expression of Mena pro-tein in GC was significantly upregulated and greatly increased in the intestinal-type and mixed-type GC than that in the diffuse-type and was negatively related to the invasion and metastasis of GC. Patients with Mena overexpression had better prognosis. The frequen-cies of the A and G alleles, as well as the AA, AG, and GG genotypes, at the Mena SNP rs3795443 locus were significantly different be-tween patients with gastric carcinoma and the control groups (OR=2.1489,95%CI 1.4607~3.1613, P<0.01). The frequencies of these five Mena gene SNP loci were not significantly related with the survival of patients with gastric carcinoma. Conclusion:The upregula-tion of Mena expression is involved in maintaining the histological phenotype, invasion, metastasis, and prognosis of gastric adenocarci-noma. Individuals with GG and AG genotypes at the Mena rs3795443 locus have increased risk of gastric carcinoma, which suggests that screening for this genotype would be helpful in assessing the genetic susceptibility of gastric carcinoma.