Open AccessLoss of gastric gland mucin‐specific O ‐glycan is associated with progression of differentiated‐type adenocarcinoma of the stomach
Author(s) -
Shiratsu Kazuo,
Higuchi Kayoko,
Nakayama Jun
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12305
Subject(s) - mucin , adenocarcinoma , immunohistochemistry , cancer , pathology , phenotype , biology , stomach , cancer research , medicine , gene , biochemistry
Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O ‐linked oligosaccharides having terminal α1,4‐linked N ‐acetylglucosamine (αGlc NA c) residues largely attached to a MUC 6 scaffold. Previously, we generated A4gnt‐deficient mice, which totally lack αGlc NA c, and showed that αGlc NA c functions as a tumor suppressor for gastric cancer. Here, to determine the clinicopathological significance of αGlc NA c in gastric carcinomas, we examined immunohistochemical expression of αGlc NA c and mucin phenotypic markers including MUC 5 AC , MUC 6, MUC 2, and CD 10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer‐specific survival. The αGlc NA c loss was evaluated in MUC 6‐positive gastric carcinoma. Thirty‐three (61.1%) of 54 differentiated‐type gastric adenocarcinomas exhibiting MUC 6 in cancer cells lacked αGlc NA c expression. Loss of αGlc NA c was significantly correlated with depth of invasion, stage, and venous invasion by differentiated‐type adenocarcinoma. Loss of αGlc NA c was also significantly associated with poorer patient prognosis in MUC 6‐positive differentiated‐type adenocarcinoma. By contrast, no significant correlation between αGlc NA c loss and any clinicopathologic variable was observed in undifferentiated‐type adenocarcinoma. Expression of MUC 6 was also significantly correlated with several clinicopathological variables in differentiated‐type adenocarcinoma. However, unlike the case with αGlc NA c, its expression showed no correlation with cancer‐specific survival in patients. In undifferentiated‐type adenocarcinoma, we observed no significant correlation between mucin phenotypic marker expression, including MUC 6, and any clinicopathologic variable. These results together indicate that loss of αGlc NA c in MUC 6‐positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma.