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ING5 can interact with p53, thereby inhibiting cell growth and inducing apoptosis. To clarify the roles of ING5 in gastric tumorigenesis and progression, its expression was examined by immunohistochemistry on a tissue microarray containing gastric nonneoplastic mucosa (n = 119), dysplasia (n = 50), and carcinomas (n = 429), with its comparison with clinicopathologic parameters of the carcinomas. ING5 expression was analyzed in gastric carcinoma tissues and cell lines (MKN28, MKN45, AGS, GT-3 TKB, and KATO-III) by Western blot and reverse transcriptase-polymerase chain reaction. ING5 protein was found to distribute to the nuclei of gastric carcinoma cells with similar messenger RNA levels. An increased expression of ING5 messenger RNA was observed in gastric carcinoma in comparison with paired mucosa (P < .05). Lower expression of nuclear ING5 was detected in gastric dysplasia and carcinoma than that in nonneoplastic mucosa (P < .05). Gastric nonneoplastic mucosa and metastatic carcinoma showed more expression of cytoplasmic ING5 than did gastric carcinoma and dysplasia (P < .05). Nuclear ING5 expression was negatively correlated with tumor size, depth of invasion, lymph node metastasis, and clinicopathologic staging (P < .05), whereas cytoplasmic ING5 was positively associated with depth of invasion, venous invasion, lymph node metastasis, and clinicopathologic staging (P < .05). Nuclear ING5 was more expressed in older than younger carcinoma patients (P < .05). There was a higher expression of nuclear ING5 in intestinal-type than diffuse-type carcinoma (P < .05), whereas it was the converse for cytoplasmic ING5 (P < .05). Survival analysis indicated that nuclear ING5 was closely linked to favorable prognosis of carcinoma patients (P < .05), albeit not independent. It was suggested that aberrant ING5 expression may contribute to pathogenesis, growth, and invasion of gastric carcinomas and could be considered as a promising marker to gauge aggressiveness and prognosis of gastric carcinoma.

Bag-1 is an antiapoptotic protein with its altered expression and localization in malignancies. To clarify the role of Bag-1 in gastric carcinogenesis, its expression was examined by immunohistochemistry and in situ hybridization on a tissue microarray containing gastric carcinomas, adjacent nonneoplastic mucosa (NNM), adenomas, intestinal metaplasia (IM), or gastritis. Gastric carcinoma tissue and cell lines were studied for Bag-1 expression by Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). The results demonstrated that Bag-1 proteins were differentially expressed in the nucleus or cytosol of MKN28, AGS, MKN45, KATO-III, or HGC-27 cell lines, despite similar levels of messenger RNA (mRNA) expression. The Bag-1 mRNA overexpression was detectable in 73.3% of 15 gastric carcinomas without significant difference in its encoding products' levels. The nuclear Bag-1 expression gradually decreased from gastritis, IM, adenoma to carcinoma (P < .05), and negatively correlated with lymphatic invasion or lymph node metastasis, cytoplasmic Bag-1 expression, negative parafibromin expression, and poor prognosis (P < .05). Cytoplasmic Bag-1 was weakly immunoreactive in carcinomas, compared with gastritis (P < .05), and positively associated with invasive depth and poor prognosis of the carcinoma (P < .05). The positive rate of Bag-1 mRNA expression was higher in adjacent IMs than carcinomas or adjacent NNM (P < .05). Bag-1 mRNA was expressed more in carcinomas from female patients than the male counterparts (P < .05). There was a positive correlation of Bag-1 mRNA expression with invasive depth and venous invasion (P < .05). Our study indicated that aberrant expression and subcellular distribution of Bag-1 might play an important role in the malignant transformation of gastric epithelial cells and should be considered as a biomarker for gastric carcinogenesis, subsequent progression, and prognosis.