Down-expression of tumor protein p53-induced nuclear protein 1 in human gastric cancer.
OBJECTIVE
Overexpression of tumor protein p53-induced nuclear protein 1 (TP53INP1) induces G1 cell cycle arrest and increases p53-mediated apoptosis. To clarify the clinical importance of TP53INP1, we analyzed TP53INP1 and p53 expression in gastric cancer.


METHODS
TP53INP1 and p53 expression were examined using immunohistochemistry in 142 cases of gastric cancer. The apoptosis of gastric cancer cells was analyzed using the TUNEL method. The relationship between the expression of TP53INP1 and clinicopathological factors was statistically analyzed.


RESULTS
TP53INP1 was expressed in 98% (139/142 cases) of non-cancerous gastric tissues and was down-expressed in 64% (91/142 cases) of gastric cancer lesions from the same patients. TP53INP1 expression was significantly decreased (43.9%) in poorly differentiated adenocarcinoma compared with well or moderately differentiated adenocarcinoma (81.6%). Cancers invading the submucosa or deeper showed lower positively (59.1%) compared with mucosal cancers (85.2%). Decrease or loss of TP53INP1 expression was significantly correlated with lymphatic invasion (54.3% vs 82.0% without lymphatic invasion) and node-positive patients (31.3% vs 68.3% in node-negative patients). P53 was expressed in 68 (47.9%) patients of gastric cancer, whereas it was absent in normal gastric tissues. A significant association was also observed between TP53INP1 status and the level of apoptosis in tumor cells: the apoptotic index in TP53INP1-positive tissues was significantly higher than that in TP53INP1-negative portions. Finally, when survival data were analyzed, loss of TP53INP1 expression had a significant effect in predicting a poor prognosis (P=0.0006).


CONCLUSIONS
TP53INP1-positive rate decreases with the progression of gastric cancer. TP53INP1 protein negativity is significantly associated with aggressive pathological phenotypes of gastric cancer. TP53INP1 is related to the apoptosis of gastric cancer cells. The decreased expression of the TP53INP1 protein may reflect the malignant grade of gastric cancer and is regarded as an adverse prognostic factor.
Jiang
Pei-Hong
PH
Department of Internal Medicine and Medical Oncology, Cancer Research Institute, Kanazawa University, Japan.
Motoo
Yoshiharu
Y
Garcia
Stéphane
S
Iovanna
Juan Lucio
JL
Pébusque
Marie-Josèphe
MJ
Sawabu
Norio
N
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000368:Aged; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D016158:Genes, p53; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D002352:Carrier Proteins; D006360:Heat-Shock Proteins; C495901:TP53 protein, human; C429767:TP53INP1 protein, human; D016159:Tumor Suppressor Protein p53