<b><i>Purpose:</i></b> To evaluate whether the European Neuroendocrine Tumor Society (ENETS) system or the 8th American Joint Committee on Cancer (AJCC) staging manual are suitable for gastric neuroendocrine carcinomas and/or mixed adenoneuroendocrine carcinomas (G-NECs/MANECs). <b><i>Methods:</i></b> Patients in a multicentric series with G-NEC/MANEC who underwent curative-intent surgical resection for a primary tumor were included. An optimal staging system was proposed base on analysis of the T and N status and validated by the SEER database. <b><i>Results:</i></b> Compared with the ENETS system, the survival curves of the T category and N category in the 8th AJCC system were better separated and distributed in a more balanced way, but the survival curves of T2 vs. T3, N0 vs. N1, and N3a vs. N3b overlapped. For the T category, the 8th AJCC T category was modified by combining T2 and T3, which was consistent with the T category in the 6th AJCC manual for GC. For the N category, the optimal cut-off values of metastatic lymph nodes using X-tile were also similar to those of the N category in the 6th AJCC system. The Kaplan-Meier plots of the 6th AJCC system showed statistically significant differences between individual substages. Compared with the other 2 classifications, the 6th AJCC system also showed superior prognostic stratification. Similar results were obtained in both multicentric and SEER validation sets. <b><i>Conclusions:</i></b> Compared to the 8th AJCC and ENETS systems, the 6th AJCC staging system for GC is more suitable for G-NEC/MANEC and can be adopted in clinical practice.

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Marfan syndrome (MFS) is an inherited and systemic disorder. It has been reported that mutations in the fibrillin-1 gene (FBN1) account for ~90% of autosomal dominant cases of MFS. This study was conducted to screen mutations of FBN1 in a Chinese family with autosomal dominant MFS; four individuals including two patients with MFS were recruited. The family members underwent complete physical, cardiovascular and ophthalmologic examinations. Genomic DNA samples were collected from the family along with 383 unrelated healthy subjects. FBN1 coding regions were amplified by polymerase chain reaction and analyzed by direct sequencing. SIFT and PolyPhen-2 were used to predict the possible structural and functional alterations of the protein. A novel heterozygous mutation c.1708 T>G (p.C570G) in exon 14 was identified, which led to a substitution of cysteine by glycine at codon 570 (p.C570G). The mutation was identified as being associated with the MFS phenotype in the affected members of this family. However, the unaffected family members and the 383 normal controls lacked the mutation. Multiple sequence alignment of the human FBN1 protein revealed that this novel mutation occurred within a highly conserved region of the FBN1 protein across different species and may induce structural alterations in this functional domain. The spectrum of MFS-associated mutations in the FBN1 gene has been enriched from this study; this may improve understanding of the molecular pathogenesis and clinical diagnosis of MFS.