%0 Generic %A Y., Tajima %A T., Murakami %A T., Saito %A T., Hiromoto %A Y., Akazawa %A N., Sasahara %A H., Mitomi %A T., Yao %A S., Watanabe %D 2017 %T Supplementary Material for: Distinct Involvement of the Sonic Hedgehog Signaling Pathway in Gastric Adenocarcinoma of Fundic Gland Type and Conventional Gastric Adenocarcinoma %U https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Distinct_Involvement_of_the_Sonic_Hedgehog_Signaling_Pathway_in_Gastric_Adenocarcinoma_of_Fundic_Gland_Type_and_Conventional_Gastric_Adenocarcinoma/5230417 %R 10.6084/m9.figshare.5230417.v1 %2 https://ndownloader.figshare.com/files/8934079 %K Gastric adenocarcinoma of fundic gland type %K Sonic hedgehog signaling pathway %K β-Catenin %K Guanine nucleotide binding protein, alpha stimulating complex %X

Background/Aims: Gastric adenocarcinoma of fundic gland type (GAFG), which is a rare variant of gastric cancer, is reportedly associated with both Wnt/β-catenin signaling activation and guanine nucleotide binding protein, alpha stimulating complex (GNAS) mutations. This study aimed to elucidate potential roles of the Sonic hedgehog (Shh) signaling pathway in GAFG. Methods: We performed immunostaining for β-catenin and Shh signal-associated proteins, including Patched (Ptch), Smoothened (Smo), and Glioma-associated oncogene-1 (Gli1), and the direct sequencing of GNAS/BRAF/KRAS in 27 GAFGs, and compared them with 30 conventional gastric adenocarcinomas (CGAs). Results: GAFGs exhibited significantly lower immunoreactivity scores for Ptch, Smo, and Gli1 than CGAs. Moreover, while the Ptch score was significantly lower in the GAFG tumor areas than in the non-neoplastic areas adjacent to GAFG, the score was significantly higher in the CGA tumor areas than in the non-neoplastic areas. Similar trends were observed in the scores for Smo and Gli1. β-Catenin expression and GNAS mutations were found in 22 (81%) and 8 (30%) of the 27 GAFGs respectively. Gli1 expression was significantly associated with mutations in GNAS. Conclusion: GAFG and CGA exhibited distinct Ptch, Smo, and Gli1 expression patterns. Downregulation of the Shh signaling pathway, as well as activation of the Wnt/β-catenin signaling pathway, may therefore be associated with tumorigenesis in GAFG.

%I Karger Publishers