Combined evaluation of expressions of p53 and p21 proteins as prognostic factors for patients with gastric carcinoma.
BACKGROUND
The tumor suppressor gene p53 is a nuclear protein which plays a key role in tumor progression by regulating DNA repair, cell division and apoptosis. One major function of wild-type p53 is to control the onset of DNA replication at the G1-S boundary by inducing p21 protein, which promotes cell cycle arrest by inhibiting the phosphorylation of the cyclin-dependent kinases' complexes and blocking cell cycle progression to the S-phase.


METHODS
195 human gastric cancer specimens were prepared for immunohistochemical staining, using antibodies against p53 and p21. Clinicopathological factors and the clinical prognosis were examined for each indicator.


RESULTS
Of those 195, positive rates of p53 and p21 were 37.9% (74/195) and 42.6% (83/195), respectively. p53-negative patients had a better 5-year survival rate compared with positive ones (p < 0.05), and p21-positive cases had better 5-year survival rate compared with negative ones (p < 0.05). Four separate groups were prepared, based on expressions of p53 and p21, and the prognoses were compared. The incidence of the p53(-)/p21(+) group was 27.2% (53/195 cases) and that of the p53(-)/p21(-), p53(+)/p21(-) and p53(+)/p21(+) groups was totally 72.8% (142/195 cases). The 5-year survival time of the former group was 67.5% and was significantly longer than the combined 5-year survival time of the latter groups of 45.9% (p < 0.05).


CONCLUSIONS
The incidence in cases where functions of either or both of p53 and p21 proteins were diminished exceeded 70% of all the cases. The survival time for the p53(-)/p21(+) group with proper functions of both proteins and the signal pathway was significantly longer. The combined evaluation of expressions of p53 and p21 proteins in gastric cancer tissues aids in predicting the clinical prognosis for surgically treated gastric cancer patients.
Okuyama
Toshiro
T
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Maehara
Yoshihiko
Y
Kabashima
Akira
A
Takahashi
Ikuo
I
Kakeji
Yoshihiro
Y
Sugimachi
Keizo
K
D000368:Aged; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53