Loss of maspin expression is associated with development and progression of gastric carcinoma with p53 abnormality.
Maspin, a serine protease inhibitor related to the serpin family, was originally identified in normal mammary epithelium. Reduced expression of maspin is related with development, invasion and metastasis of certain human cancers. In the present study, the expression of maspin was examined in gastric mucosa, adenoma and carcinoma by immunohistochemistry and RT-PCR. In non-neoplastic mucosa, maspin was expressed in cytoplasm and cell membrane of foveolar epithelia, fundic glandular cells and pyloric glandular cells. Maspin expression was lost in 71% (71/100) of gastric carcinomas, and in 19% (4/21) of adenomas, respectively. Loss of maspin expression was significantly associated with poorly differentiated histology, advanced stage and deep invasion (P<0.001). There was an inverse correlation between maspin expression and abnormal p53 accumulation. Maspin mRNA expression was lost in all of 8 gastric carcinoma cell lines that was retrieved after treatment with demethylation agent 5-aza-2'-deoxycytidine in 5 of 8 cell lines. These results suggest that loss of maspin expression partly due to DNA methylation may participate in tumor development and progression of gastric carcinoma in relation with p53 pathway. Loss of maspin expression may serve as a biological marker of high-grade malignancy.
Ito
Reiko
R
Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Nakayama
Hirofumi
H
Yoshida
Kazuhiro
K
Oda
Noriko
N
Yasui
Wataru
W
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019175:DNA Methylation; D000077209:Decitabine; D018450:Disease Progression; D005753:Gastric Mucosa / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D011506:Proteins; D012333:RNA, Messenger; C085344:SERPIN-B5; D015843:Serpins; D016159:Tumor Suppressor Protein p53; D000077209:Decitabine; D001374:Azacitidine