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

Zheng, Hua-chuan; Xu, Xiao-yan; Xing, Ya-nan; Wei, Zheng-li; Takahashi, Hiroyuki; Masuda, Shinji; Takano, Yasuo

doi:10.1016/j.humpath.2009.10.017

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Volume 41, Issue 5 , Pages 724-736, May 2010

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

Hua-chuan Zheng, MD, PhD
- Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, 110001 China
- Corresponding author.
Xiao-yan Xu, PhD
- Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, 110001 China
Ya-nan Xing, MD
- Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, 110001 China
Zheng-li Wei, MD, PhD
- Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, 110001 China
Hiroyuki Takahashi, MD, PhD
- Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, 930-0194 Japan
Shinji Masuda, MD, PhD
- Kouseiren Takaoka Hospital, Takaoka, 933-8555 Japan
Yasuo Takano, MD, PhD
- Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, 930-0194 Japan

Received 13 July 2009; received in revised form 15 October 2009; accepted 22 October 2009. published online 25 January 2010.

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.