Apoptosis and cell proliferation in the development of gastric carcinomas: associations with c-myc and p53 protein expression.
OBJECTIVE
Patients with gastric carcinomas have a poor prognosis and low survival rates. The aim of the present paper was to characterize cellular and molecular properties to provide insight into aspects of tumor progression in early compared with advanced gastric cancers.


METHODS
One hundred and nine graded gastric carcinomas (early or advanced stage, undifferentiated or differentiated type) with paired non-cancer tissue were studied to define the correlation between apoptosis (morphology, terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling), cell proliferation (Ki-67 expression, morphology) and expression and localization of two proteins frequently having altered expression in cancers, namely p53 and c-myc.


RESULTS
Overall, apoptosis was lower in early stage, differentiated and undifferentiated gastric carcinomas compared with advanced-stage cancers. Cell proliferation was comparatively high in all stages. There was a high level of p53 positivity in all stages. Only the early- and advanced-stage undifferentiated cancers that were p53 positive had a significantly higher level of apoptosis (P < 0.05). Cell proliferation was significantly greater (P < 0.05) only in the early undifferentiated cancers that had either c-myc or p53-positivity.


CONCLUSIONS
The results indicate that low apoptosis and high cell proliferation combine to drive gastric cancer development. The molecular controls for high cell proliferation of the early stage undifferentiated gastric cancers involve overexpression of both p53 and c-myc. Overexpression of p53 may also control cancer development in that its expression is associated with higher levels of apoptosis in early and late-stage undifferentiated, cancers.
Ishii
Hideaki H
HH
Second Department of Pathology, Tokyo Medical University, Japan. hhishii@tokyo-med.ac.jp
Gobé
Glenda C
GC
Pan
Wenshen
W
Yoneyama
Juichi
J
Ebihara
Yoshiro
Y
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000951:Antigens, Neoplasm / Q000378:metabolism; D017209:Apoptosis; D002455:Cell Division; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D009367:Neoplasm Staging; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D000951:Antigens, Neoplasm; D019394:Ki-67 Antigen; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53