The Morphological Features of “Cavitary” Type Angiogenesis in Diffuse and Intestinal Types of Gastric Cancer and Its Relationship with Tumor-Infiltrating Immune Cells.

Background: Previously we have described the "cavitary” type of angiogenesis by gastric cancer (GC) consisting of the formation of “cavitary structures” (CS) in tumor stroma, which are then lined by endothelial cells and merged into the blood vessels of the organ. The morphological features of the "cavitary” type of angiogenesis in intestinal and diffuse types of GC and the relations of CS with the tumor-infiltrating immune cells, was the purpose of this study. Materials and Methods: The samples of tumor and adjacent gastric mucosa (GM) in 73 patients with GC who had undergone radical surgery were being studied. The sections were stained with hematoxylin and eosin and immunohistochemically using antibodies to CD34, CD4, CD8, CD20 и CD68. Results: The differences of “cavitary” type of angiogenesis in the intestinal and diffuse types of GC are only associated with CS type-1 that are formed as a result of the abruption of epithelial cells from the underlying stroma. In the intestinal type of GC the basis for the formation of CS type-1 are the tumor glands. The wall of such CS is most likely the basement membrane bordering the connective tissue. In the diffuse type of GC the CS type-1 are presented as the structures limited from outside by the tumor cells. In their lumen the fragments of tumor tissue having the same structure as the surrounding one are being detected. The performed analysis showed that the number of CS type-1 was associated with the density of CD68, whereas the presence of CS type-2 – with the presence of lymphoid follicles (LF) and B-cell infiltrations at the boundary of tumor and GM. The density of CD68 in GM was higher in cases with multiple CS type-1 (72.6±47.0 vs. 41.6±15.4 cells per unit area, P= .03). In turn, CS type-2 were more often met in the presence of multiple LF (72,3% vs. 33,3%, P= ,04) and B-cell infiltrations (90% vs. 26,3%, P= ,001). Conclusion: The obtained data testify about the relation of CD20 lymphocytes and CD68 macrophages with the "cavitary” type of angiogenesis.

Portal and Peripheral Blood Levels of Tumor Markers in Patients with Gastric Cancer

BACKGROUND: Correlations between the AFP, CEA, CA19-9, and CA125 levels of portal and peripheral blood were examined in 42 patients (male, 29; female, 13; mean age, 55.9) with gastric cancer in order to identify a better blood sample for measuring these tumor markers. METHODS: The levels of these tumor markers were measured by the immunoradiometric assay. The cut-off levels of positivity were 6 ng/ml for AFP, 7 ng/ml for CEA, 25 U/ml for CA19-9, and 35 U/ml for CA125. RESULTS: The positive rates of AFP, CEA, CA19-9, and CA125 were 11.9%, 19.0%, 14.3%, and 7.1% in portal blood and 9.5%, 19.0%, 14.3%, and 4.8% in peripheral blood, respectively. The positive rate of portal venous CEA was significantly higher in cases with lymph node metastasis, distant metastasis, and lymphatic invasion than those without these variables. The positive rate of peripheral venous CEA was significantly higher in cases with lymph node metastasis, distant metastasis, high stages, and large tumor size. The positive rate of peripheral venous CA19-9 was higher in cases with distant metastasis. The positive rate of CA125 in portal and peripheral blood was higher in cases of lymphatic invasion. Neither portal nor peripheral AFP correlated with pathologic factors. Regression analysis revealed that the portal venous levels of AFP, CEA, CA19-9, and CA125 could be estimated by using the peripheral venous levels of these tumor markers. CONCLUSION: We can avoid intraoperative sampling of portal blood to measure the portal venous levels of AFP, CEA, CA19-9, and CA125 because the peripheral venous level of these tumor markers reflects the portal venous levels. The measurement of peripheral venous levels of CEA and CA19-9 can be used as non-anatomical prognostic indicators for staging of gastric cancer.

CEA and CA19-9 in the Tissue, Portal, and Peripheral Blood of Gastric Cancer Patients

BACKGROUND: To clarify the clinical significance of CEA and CA19-9 in patients with gastric cancer, we evaluated the correlation between tissue expression, the peripheral and the portal levels of these tumor markers, and ten clinicopathological factors, as well as the prognosis. METHODS: Surgical specimens from 40 patients with gastric cancer were examined by using immunohistochemical staining with anti-CEA and anti-CA19-9 monoclonal antibodies. Serum levels of CEA and CA19-9 in the portal and the peripheral blood were measured by using immunoradiometric assays. RESULTS: Positive values of the portal venous CEA were more common in patients with lymph-node metastasis, distant metastasis, and lymphatic invasion than in those without these factors. Curative surgery was performed in 50.5% of the patients with high portal CEA levels and in 90.6% of the patients with low portal CEA levels. Positive values of the peripheral venous CEA were significantly higher in cases with lymph-node metastasis. The positive rate of CA19-9 immunohistochemistry was significantly higher in patients with distant metastasis and in non-curative surgery. The positive rate of peripheral venous CA19-9 was higher in cases with distant metastasis. The three-year survival rate of patients with negative tissue CEA was significantly higher than that of patients with a positive result. The peripheral venous levels of CEA and CA19-9 reflected the portal venous levels accurately. CONCLUSIONS: These results suggest that immunohistochemical examination of CEA in patients with gastric cancer is useful for the evaluation of the biological aggressiveness and progression of the disease and can be used for making a prognosis.