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. 2008 Feb;452(2):147-55.
doi: 10.1007/s00428-007-0551-z. Epub 2007 Dec 14.

Downregulated parafibromin expression is a promising marker for pathogenesis, invasion, metastasis and prognosis of gastric carcinomas

Hua-Chuan Zheng  1 , Hiroyuki Takahashi, Xiao-Han Li, Takuo Hara, Shinji Masuda, Yi-Fu Guan, Yasuo Takano
Affiliations

Downregulated parafibromin expression is a promising marker for pathogenesis, invasion, metastasis and prognosis of gastric carcinomas

Hua-Chuan Zheng et al. Virchows Arch. 2008 Feb.

Abstract

Parafibromin is a protein encoded by the hyperparathyroidism 2 oncosuppressor gene and its downregulated expression is involved in pathogenesis of parathyroid carcinomas. To clarify the roles of parafibromin expression in tumourigenesis and progression of gastric carcinomas, it was examined by immunohistochemistry (IHC) on tissue microarray containing gastric carcinomas (n = 508), adenomas (n = 45) and gastritis (n = 49) with a comparison of its expression with clinicopathological parametres of carcinomas. Gastric carcinoma cell lines (MKN28, AGS, MKN45, KATO-III and HGC-27) were studied for parafibromin expression by IHC and western blot. Parafibromin expression was localised in the nucleus of gastric epithelial cells, adenoma, carcinoma cells and cell lines. Its expression was gradually decreased from gastritis to gastric carcinoma, through gastric adenomas (p < 0.05) and inversely correlated with tumour size, depth of invasion, lymphatic invasion, lymph node metastasis and Union Internationale Contre le Cancer (UICC) staging (p < 0.05) but not with sex or venous invasion (p > 0.05). Parafibromin was strongly expressed in older carcinoma patients compared with younger ones (p < 0.05). There was stronger positivity of parafibromin in intestinal-type than diffuse-type carcinomas (p < 0.05). Univariate analysis indicated cumulative survival rate of patients with positive parafibromin expression to be higher than without its expression (p < 0.05). Multivariate analysis showed that age, tumour size, depth of invasion, lymphatic invasion, lymph node metastasis, UICC staging and Lauren's classification but not sex, venous invasion or parafibromin expression were independent prognostic factors for carcinomas(p < 0.05). Downregulated parafibromin expression possibly contributed to pathogenesis, growth, invasion and metastasis of gastric carcinomas. It was considered as a promising marker to indicate the aggressive behaviours and prognosis of gastric carcinomas.

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Figures

Fig. 1
Fig. 1
Parafibromin expression in gastric carcinoma cell lines. a Parafibromin was positively immunostained in the nucleus of MKN28 (a), AGS (b), MKN45 (c), KATO-III (d) and HGC-27(e). b Cell lysate (50 µg) was loaded and probed with anti-human parafibromin antibody (60 kd) with β-actin (42 kd) as an internal control. Lane #1: MKN28; #2 AGS; #3 MKN45; #4 KATO-III; #5 HGC-27
Fig. 2
Fig. 2
Immunohistochemical staining of parafibromin in gastritis, adenoma and carcinoma. Note parafibromin positivity was strongly observed in the nucleus of gastric superficial epithelium (a), and adenoma (c) and early gastric carcinoma (b), occasionally weaker in the stromal fibroblasts and lymphocytes(a, c), but not in given advanced gastric carcinomas (d), indicating that the internal positive control (stromal cells) was negative adjacent to the negative staining carcinoma cells but positive adjacent to the positive epithelial cells
Fig. 3
Fig. 3
Correlation between parafibromin status and prognosis of the gastric carcinoma patients. Kaplan–Meier curves for cumulative survival rate of patients with gastric carcinomas according to the parafibromin expression in overall (a), early (b, EGC) and advanced (c, AGC) gastric carcinomas
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