Nuclear or cytoplasmic localization of Bag-1 distinctly correlates with pathologic behavior and outcome of gastric carcinomas

• Published in: Human pathology 2010-05, Vol.41 (5), p.724-736
• Main Authors: Zheng, Hua-chuan, MD, PhD, Xu, Xiao-yan, PhD, Xing, Ya-nan, MD, Wei, Zheng-li, MD, PhD, Takahashi, Hiroyuki, MD, PhD, Masuda, Shinji, MD, PhD, Takano, Yasuo, MD, PhD
• Format: Article
• Language: English
• Subjects: Adenoma - genetics; Adenoma - metabolism; Adenoma - pathology; Apoptosis; Bag-1; Behavior; Biological and medical sciences; Biomarkers, Tumor - metabolism; Blotting, Western; Carcinoma - genetics; Carcinoma - metabolism; Carcinoma - pathology; Cell cycle; Cell Line; Cell Nucleus - metabolism; Cell Nucleus - pathology; Cells, Cultured; Cytoplasm - metabolism; Cytoplasm - pathology; Disease Progression; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Female; Gastric carcinoma; Gastritis - genetics; Gastritis - metabolism; Gastritis - pathology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Kaplan-Meier Estimate; Kinases; Male; Medical sciences; Metaplasia - genetics; Metaplasia - metabolism; Metaplasia - pathology; Multivariate analysis; Pathobiologic behavior; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Prognosis; Proportional Hazards Models; Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA polymerase; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Transcription Factors - genetics; Transcription Factors - metabolism; Tumors
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2009.10.017

Summary 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.