Paradoxical expression of maspin in gastric carcinomas: correlation with carcinogenesis and progression.
Maspin, a serine protease inhibitor related to the serpin family, can suppress invasion and metastasis of malignancies. To clarify the role of maspin in the genesis and progression of gastric carcinomas, its expression pattern and level were studied by immunohistochemistry on tissue microarrays containing gastric carcinoma (n = 237), normal gastric mucosa (n = 23), intestinal metaplasia (n = 38), and adenoma (n = 42); and the findings were compared with clinicopathological parameters. Furthermore, maspin expression in the gastric carcinoma cell lines (HCG-27, MKN28, and MKN45) was examined by immunohistochemistry and Western blotting. We found that cytoplasmic and nuclear maspin expression paralleled each other (P < .05) and decreased from intestinal metaplasia, adenoma, and carcinoma to normal gastric mucosa (P < .05). A significant positive association was noted with depth of invasion, lymphatic invasion, lymph node metastasis, and TNM stage (P < .05) but not with sex or Lauren's classification (P > .05). Univariate and multivariate analyses indicated that expression of maspin correlated negatively with cumulative patient survival in gastric carcinoma (P < .05) but was not an independent factor in the prognosis. The 2 independent factors, depth of invasion and lymphatic invasion, influenced the relation between nuclear maspin expression and survival, whereas only depth of invasion correlated with cytoplasmic maspin. Our study indicated that maspin expression experiences upregulation in gastric precancerous lesions and then slight downregulation with malignant transformation. High expression may paradoxically promote invasion and metastasis of gastric carcinomas and could be considered a good marker for the pathobiological behaviors of gastric carcinomas.
Yu
Miao
M
Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Sugitani, Toyama 2630, Japan.
Zheng
Huachuan
H
Tsuneyama
Koichi
K
Takahashi
Hiroyuki
H
Nomoto
Kazuhiro
K
Xu
Huimian
H
Takano
Yasuo
Y
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D000236:Adenoma / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology*; D015843:Serpins / Q000378:metabolism*; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; C085344:SERPIN-B5; D015843:Serpins