Low expression of FHIT and PTEN correlates with malignancy of gastric carcinomas: tissue-array findings.
To clarify the roles of FHIT (fragile histidine triad) and PTEN (phosphatase and tensin homology deleted from human chromosome 10) expression in the genesis and progression of gastric cancers, we examined expression of FHIT and PTEN on tissue microarray containing gastric normal mucosa (n=49), adenoma (n=49), noncancerous mucosa adjacent to carcinoma (n=84) and carcinoma (n=249) by immunohistochemistry. Their expression was compared with clinicopathologic parameters of tumors, including expression of p53 and cysteine protease protein 32 as well as survival time of patients with carcinoma. The results showed expression of FHIT and PTEN were lower in gastric carcinoma than those in normal mucosa, noncancerous mucosa adjacent to carcinoma and adenoma of the stomach (P<0.05). FHIT and PTEN expression showed a significantly negative association with depth of invasion, lymphatic invasion, and lymph node metastasis, liver metastasis, and Union Internationale Contre le Cancer staging of gastric carcinoma (P<0.05). Intestinal-type gastric carcinomas highly expressed FHIT and PTEN protein, compared with diffuse-type ones (P<0.05). Expression of FHIT and PTEN were positively related with expression of p53 and cysteine protease protein 32 in gastric carcinoma (P<0.05), as well as favorable prognosis of the patients with the tumors (P<0.05). There was positive relationship between FHIT and PTEN expression in gastric carcinoma (P<0.05). It was suggested that down-regulated expression of FHIT and PTEN contributed to gastric carcinogenesis possibly by involving in the imbalance between apoptosis and proliferation of cells. Their altered expression underlay the molecular basis of invasion, metastasis, differentiation of gastric carcinoma.
Zheng
Huachuan
H
Department of Pathology (1), School of Medicine, University of Toyama, Sugitani 2630, Toyama, Japan.
Takahashi
Hiroyuki
H
Murai
Yoshihiro
Y
Cui
Zhengguo
Z
Nomoto
Kazuhiro
K
Tsuneyama
Koichi
K
Takano
Yasuo
Y
D017766:Acid Anhydride Hydrolases / Q000032:analysis / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism*; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000032:analysis / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D046888:Tissue Array Analysis; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D051059:PTEN Phosphohydrolase; D000099170:Bis(5'-adenosyl)triphosphatase; C494929:PTEN protein, human