Immunohistochemical expression of P15 (INK4B) and SMAD4 in advanced gastric cancer.
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.


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).


CONCLUSIONS
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.
Sakellariou
Stratigoula
S
Pathology Department, G. Gennimatas Hospital, Papagou, Athens, Greece. 7791j@otenet.gr
Liakakos
Theodore
T
Ghiconti
Ioanna
I
Hadjikokolis
Stamatis
S
Nakopoulou
Lydia
L
Pavlakis
Kitty
K
D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051901:Smad4 Protein / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D051901:Smad4 Protein