Seprase, a membrane-type serine protease, has different expression patterns in intestinal- and diffuse-type gastric cancer.
OBJECTIVE
Seprase is an integral membrane serine proteinase with gelatinase activity that may be involved in cancer invasion and metastasis. However, the pathophysiologic significance of its expression in gastric cancer tissue has not been fully elucidated.


METHODS
Seprase expression and distribution in gastric cancer specimens obtained from 133 patients were examined by immunohistochemistry and immunoblotting.


RESULTS
Immunohistochemistry showed that in intestinal-type cancer, which includes well and moderately differentiated adenocarcinoma, seprase immunoreactivity was mainly recognized in the moderately differentiated cells and not in the well differentiated cells. In the diffuse type, which includes poorly differentiated adenocarcinoma and signet ring cell carcinoma, seprase immunoreactivity was seen mainly in cells with poor cell-to-cell junctions. The reactive pattern in the cells was different between moderately differentiated adenocarcinoma and diffuse-type carcinoma. Besides the cytoplasm, the cell membrane also apparently reacted in the former, while only the cytoplasm reacted diffusely in the latter. Seprase immunoreactivity was also recognized in endothelial cells and stromal cells especially adjacent to tumor nests. The immunoreactivity of the stromal cells was more abundant in the intestinal type than in the diffuse type, and these stromal expressions of seprase in the intestinal type correlated with the liver (13/13 = 100% of cases with metastases) or lymph node metastases (33/34 = 97% of cases with metastases). Immunoblotting showed that the levels of seprase protein were higher in intestinal-type cancer than in diffuse-type cancer.


CONCLUSIONS
These results suggested that there is a difference in seprase expression between intestinal- and diffuse-type gastric cancer; this difference may reflect distinct biological features of these types of cancer.
Okada
Kyoko
K
First Department of Pathology, Yamanashi University Faculty of Medicine, Tamaho, Nakakoma-gun, Yamanashi, Japan.
Chen
Wen-Tien
WT
Iwasa
Satoshi
S
Jin
Xin
X
Yamane
Tetsu
T
Ooi
Akishi
A
Mitsumata
Masako
M
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D010450:Endopeptidases; D005109:Extracellular Matrix / Q000201:enzymology; D005260:Female; D018093:Gelatinases / Q000032:analysis*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011237:Predictive Value of Tests; D012697:Serine Endopeptidases; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology*; D000099167:Fibroblast Activation Protein Alpha
D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha