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Updated: Jul 4, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Immunohistochemical expression of P15 (INK4B) and SMAD4 in advanced gastric cancer
Stratigoula Sakellariou1, Theodore Liakakos, Ioanna Ghiconti
1Pathology Department, G. Gennimatas Hospital, Papagou, Athens, Greece. 7791j@otenet.gr
Background:
P15 (a cyclin- D- kinase inhibitor) and SMAD4 (a signal transducer of the TGF-beta pathway) are two closely related proteins which may have an important role in gastric carcinogenesis.
Materials And Methods:
Sixty-three gastric carcinomas were studied. P15 and SMAD4 immunohistochemical expression was assessed with the DCS114.1 and BC/B8 mouse monoclonal antibodies, respectively. The results were tested for correlation with several clinicopathological parameters and patient survival.
Results:
Fifteen out of the 18 (83%) P15-positive tumors also exhibited preserved SMAD4 positivity (p = 0.001). Loss of P15 expression was more frequent in the intestinal type of carcinoma (p = 0.047). The survival rates were significantly higher for patients with reduced SMAD4 expression, in cases of well- or moderately differentiated tumors (p = 0.042).
Conclusion:
P15 gene silencing might be an important event in the tumorigenesis of gastric adenocarcinomas of the intestinal type. Smad4 may behave as a tumor promoter in low grade tumors. The observed association between P15 and SMAD4 expression supports the inductive role of Smad4 in p15 transcription.
