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BACKGROUND 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. METHODS Amplification and overexpression of c-met and c-erb B-2 were investigated retrospectively in 128 gastric carcinoma patients by using immunohistochemistry and Southern blot hybridization. Survival analysis was performed with the Kaplan–Meier test, and the log rank test was used for statistical analysis. RESULTS Overexpression of c-met and c-erb B-2 was observed in 46.1% and 16.4% of gastric carcinoma cases, respectively. Gene amplification of c-met and c-erb B-2 was detected in 10.2% and 11.7% of gastric carcinoma cases, respectively. Amplification and overexpression of c-met were correlated significantly with depth of tumor invasion and lymph node metastasis, whereas amplification and overexpression of c-erb B-2 were correlated significantly with histologic type. The survival rate of patients with amplification and/or overexpression of c-met or c-erb B-2 was significantly poorer than that of patients with no amplification or overexpression. Multivariate analysis revealed that c-met overexpression and lymph node metastasis were independent prognostic factors. CONCLUSIONS These data suggest that overexpression and/or gene amplification of c-met and c-erb B-2 may be prognostic factors in gastric carcinoma. Cancer 1999;85:1894–902. © 1999 American Cancer Society.

BACKGROUND. It has been suggested that CD44 splice variants play a role in the progression of certain epithelial cancers and non-Hodgkin's lymphoma. In this study, we investigated the epithelial variant/hematopoietic variant (E/H) ratio (the amount of the CD44 epithelial variant transcript relative to the CD44 hematopoietic variant transcript) in human gastric carcinoma compared with normal gastric mucosa. METHODS. The ratio was determined for tumors and adjacent noncancerous mucosa from 30 gastric carcinoma patients using reverse transcription-polymerase chain reaction and Southern blotting. We also determined the tumor (T)E/H-noncancerous mucosa [N)E/H (the difference between E/H ratios of tumor tissue and adjacent noncancerous mucosa) and examined these measurements for correlations with the pathologic features of gastric carcinoma, as well as for their usefulness as an indicator of tumor progression. RESULTS. The E/H ratio in tumor tissue was significantly higher than in adjacent noncancerous mucosa (P < 0.01). The TE/H - NE/H in patients with lymph node metastases was 0.16 ± 0.11, compared with 0.07 ± 0.08 in cases without lymph node metastases (P < 0.05). Significant correlations also were observed between the TE/H - NE/H and the depth of invasion, blood vessel invasion, and lymphatic vessel invasion (P < 0.03, P < 0.03, and P < 0.01, respectively). CONCLUSIONS. Our results suggest that increases in the E/H ratio may be a useful indicator of progression in gastric carcinoma.

Background. Several studies have revealed a correlation between sialosyl Tn antigen (STN) and certain clinicopathologic features of various cancers, and that STN is an independent prognostic factor. However, the clinical significance of the expression of STN in gastric cancer has not been reported. Thus, the purpose of this study was to evaluate immunohistochemically the clinical significance of expression of STN in gastric cancer. Methods. The expression of STN in surgically resected specimens of human gastric cancer was evaluated immunohistochemically using a monoclonal antibody (TKH-2), in 60 patients whose serum STN levels were measured and in 54 patients with advanced cancer who had been followed for more than 5 years after gastrectomy. The correlations between the level of STN expression and clinicopathologic factors were analyzed. The staining intensity was graded as follows :(-),less than 5% of the cancer cells expressed STN ;(+), 5-50% ;(++), more than 50%. Results. Sialosyl TN antigen staining was detected mainly on the cell membrane, in the cytoplasm, and in the luminal contents, and 57.2% of the 60 specimens expressed STN, whereas the corresponding value for positive serum levels was 15%. A higher percentage of advanced tumors expressed STN than did the early cases, but the difference was not statistically significant. All cases with strong staining, the (++) cases, were advanced cases either with lymph node metastases or with cancer invading in or beyond the muscle layer proper. The expression of STN appeared to be related to the clinical stage, the extent of cancer invasion, and the presence of lymph node metastases. Sialosyl TN antigen was detected in the serum in less than 6% of the patients whose tumors were (-) or (+) for STN expression, and in 86.7% of the patients whose tumors expressed high levels of STN (++). The estimated 5-year survival in advanced cases (Stage III) was significantly better in those with negative STN expression than in those with positive STN expression (P < 0.01). Conclusions. These results suggest that STN may be a useful marker associated with the prognosis of patients with advanced gastric cancer.

BACKGROUND Cyclins and wild-type p53 are prime cell cycle regulators and may be involved in tumorigenesis. Cyclin E is a late G1 cyclin and its abnormalities have been reported in several cancers. The authors investigated the correlation between cyclin E expression and progression of gastric carcinoma. METHODS The expression of cyclin E and p53 proteins was investigated retrospectively in 116 patients with gastric carcinoma. Immunohistochemical staining of the paraffin sections was performed using monoclonal antibodies to cyclin E and p53. RESULTS The total cyclin E positive rate was 44.0% (51 of 116) of all cases, 26 of which were strongly positive. Strong cyclin E expression frequently was observed in deeply invasive tumors, tumors with lymph node metastasis, and tumors of advanced stage. The incidence of p53 expression was higher in the cyclin E positive tumors than in the other tumors. With regard to prognosis, patients whose tumors had both strong positivity for cyclin E and positivity for p53 had significantly poorer prognosis. In multivariate analysis, the combined variable of cyclin E and p53 was an independent prognostic indicator together with serosal invasion and tumor size. CONCLUSIONS These data suggest the cyclin E expression correlates with p53 expression and may contribute to the progression of gastric carcinoma. The combined variable of cyclin E and p53 expression could be a useful prognostic indicator in patients with gastric carcinoma. Cancer 1998;82:1238-43. © 1998 American Cancer Society.

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. Methods. The expression of E-cadherin was immunohistochemically analyzed using antihuman E-cadherin antibody in 121 cases of human gastric carcinoma. Results. In noncancerous areas, the epithelial cells, including those with intestinal metaplasia, were stained positively in the plasma membrane. In contrast, E-cadherin expression of the cancer cells varied from case to case in primary and secondary sites. Tumors with a decrease in E-cadherin occurred significantly more frequently in undifferentiated adenocarcinoma (P < 0.05) and scirrhous type (P < 0.01). The rate of E-cadherin-negative tumors was higher in patients with peritoneal metastasis (P < 0.01) or in those with distant lymph node metastasis (P < 0.01), though the tumors with liver metastasis had relatively positive E-cadherin expression. Patterns of initial recurrence had similar results. Reduction or loss of E-cadherin expression correlated with shorter survival in patients after curative operation regardless of stage of disease. Conclusions. The decreased E-cadherin expression correlates with dedifferentiation, infiltrative tumor growth, distant metastasis, and poor survival for patients with gastric carcinoma. Thus, immunohistochemical study of E-cadherin may have clinicopathologic value for patients with gastric carcinoma. Cancer 1995; 76:2193–201.

Two cases of malignant rhabdoid tumor of the kidney (MRT) and two cases of bone metastasizing renal tumor (BMRT) were studied using electron microscopy and immunohistochemitry, in an attempt to evaluate the histogenetic relation to classical Wilms' tumor (2 cases). The two cases of MRT showed ultrastructural features of intermediate filament clusters in the cytoplasm. Vimentin, keratin, laminin, and peanut (PNA) lectin were immunohistochemically demonstrated in two cases of MRT. Tissue polypeptide antigen (TPA) was detected in one case. As for BMRT, the metastatic lesion exhibited numerous rosette-like structures of tumor cells. Vimentin was immunohistochemically demonstrated in one case, but no other antibodies were stained in two cases. Two cases of classical Wilms' tumor immunohistochemically demonstrated vimentin, keratin, PNA lectin, and TPA. MRT and BMRT fall within the broad spectrum of Wilms' tumors from the histogenetic aspect, but their clinical behavior is distinct. Cancer 59:963-971, 1987.