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.
Pathology Department, G. Gennimatas Hospital, Papagou, Athens, Greece. 7791j@otenet.gr
Stratigoula
S
Sakellariou
Theodore
T
Liakakos
Ioanna
I
Ghiconti
Stamatis
S
Hadjikokolis
Lydia
L
Nakopoulou
Kitty
K
Pavlakis
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