Mitsutoshi Tatsumi

The prognostic significance of amplification and overexpression of c‐met and c‐erb B‐2 in human gastric carcinomas

The c‐met and the c‐erb B‐2 protooncogenes belong to a family of tyrosine kinase growth factor receptors. Abnormalities of these oncogenes and protein products have been reported in several cancers. The authors investigated the correlation between clinical factors and amplification or overexpression of the c‐met and/or c‐erb B‐2 gene in Japanese patients with gastric carcinoma patients, with a focus on prognostic significance.

Clinicopathologic evaluation of immunohistochemical E-cadherin expression in human gastric carcinomas.

Background. E‐cadherin plays a crucial role in cell‐cell adhesion in epithelial tissues. Recent studies have shown a correlation between decreased E‐cadherin expression and cancer cell detachment.

Characteristics and clinical outcome of proximal-third gastric cancer

BACKGROUND It is generally accepted that the prognosis of patients with proximal gastric cancer (PGC) is worse than that of patients with more distal gastric cancer. STUDY DESIGN The aim of this study was to compare the clinical features and outcomes of PGC with those of middle- and distal-third gastric cancers. A total of 646 primary gastric cancers was analyzed as a retrospective study. RESULTS Proximal gastric cancer occurred in 21.8% of the 646 cancers analyzed, and approximately 21% of PGCs had esophageal invasion. The 5-year survival rate for patients with PGC was significantly lower than that of patients with more distal tumors. When the PGC group was divided into patients with esophageal invasion and without esophageal invasion, patients with esophageal invasion had significantly worse outcomes. When corrected for depth of invasion, lesions with esophageal invasion had significantly worse outcomes than those of other sites in T2 curative cancers. Proximal gastric cancer with esophageal invasion was characterized by a larger tumor, deeper penetration, and a higher incidence of lymph node metastasis compared with tumors in other sites, and in multivariate analysis of all curative cases, these variables were independent prognostic factors for survival. The frequency of positive proximal margins of PGC was higher than those of other sites. CONCLUSIONS The relatively poor prognosis associated with PGC is mainly from advanced tumor stages of esophageal invasion. Early detection is the most important strategy to improve the survival of patients with PGC. In addition, aggressive lymph node dissection and chemotherapy for esophageal invasion should be considered even if the tumor invasion is moderate (T2 tumor), and a tumor-free margin is important.

Antisense epidermal growth factor receptor delivered by adenoviral vector blocks tumor growth in human gastric cancer

Epidermal growth factor receptor (EGFR) protein overexpression is commonly found in human gastric cancer, and its gene amplification is known to correlate with poor prognosis in gastric cancer patients. With regard to therapy trials targeting EGFR, it has been reported that stable transfection of EGFR antisense or treatment with antibody against EGFR results in growth suppression of human cancer cells that express high levels of EGFR. We have designed an adenovirus-expressing antisense EGFR and have investigated its effect on the growth of gastric cancer in vitro and in vivo. Following infection with EGFR antisense RNA-expressing adenovirus (Ad-EAS), the cell surface EGFR protein levels of infected cancer cells were markedly reduced, and the in vitro growth of Ad-EAS-infected cells was significantly inhibited relative to control-infected cells in all three gastric cancer cell lines (AGS, KKLS, and MKN28) studied here (P < .0002). In a nude mouse subcutaneous tumor system, in vivo tumor growth of MKN28 was significantly inhibited after Ad-EAS treatment, and inhibition on day 48 was 93% by volume compared with that of untreated controls. These results suggest that an adenoviral vector system targeting the down-regulation of EGFR could be a good candidate for the therapy of gastric cancers that overexpress EGFR.

Immunohistochemical expression of the sialyl Lewis x antigen on gastric cancer cells correlates with the presence of liver metastasis.

The expression of the sialyl Lewis x antigen (sLe x ) on surgical specimens of primary gastric cancer corre-lates with the degree of differentiation and synchronous and metachronous liver metastasis. Multivariate analysis by means of Quantification theory II revealed that sLe x expression was an independent risk factor for liver metastasis from gastric cancer.© Kluwer Academic Publishers 1998