Expression of BMP-7 in human gastric cancer and its clinical significance.

BACKGROUND: Bone morphogenetic protein-7 (BMP-7) is a signalling molecule belonging to the transforming growth factor--superfamily. Recent studies have demonstrated the clinical impact of BMP-7 expression in various human cancers. However, there have been few reports detailing this in gastric cancer. METHODS: We immunohistochemically investigated the expression of BMP-7 in 233 gastric cancer patients to disclose the clinicopathological features of BMP-7-positive gastric cancer. RESULTS: Immunohistochemically, in human gastric cancer, BMP-7 expression was identified in cellular membranes but also in the cytoplasm of cancer cells. Bone morphogenetic protein-7-positive expression was found in 129 of 233 patients (55%). Bone morphogenetic protein-7 expression was correlated with tumour size, nodal involvement, lymphatic invasion, venous invasion and histology (P<0.05). Bone morphogenetic protein-7 expression was significantly correlated with patient postoperative outcome, especially in the undifferentiated group. Multivariate analysis revealed BMP-7 expression as one of the independent prognostic factors next to the depth of invasion and nodal involvement (P<0.01). CONCLUSIONS: From the data collected, it would be appropriate to conclude on the possible regulation of gastric cancer progression by autocrine or paracrine BMP-7 loops. We can use BMP-7 expression as one of the strong predictors of risk of tumour recurrence in gastric cancer.

CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer.

Although CD133 has been shown to be a marker for cancer stem cells in various tumours, its expression in pancreatic cancer has not yet been clinically reported. In this study, we investigated the relationship between CD133 expression and clinicopathological factors in pancreatic cancer. Pancreatic head carcinoma specimens from 80 patients who underwent surgical resection were immunohistochemically assessed for CD133, vascular endothelial growth factor (VEGF)-C, CXCR4, CD34, Ki-67, and cytokeratin (CK) expressions. Sixty percentage (48/80) of specimens were CD133-positive, with less than 15% cells per specimen expressing the marker. CD133-positive cells were found at the peripheral site of adenocarcinoma glandular structures and were negative for CK. There was a significant correlation between CD133 expression and clinicopathological factors, including histological type, lymphatic invasion, and lymph node metastasis (P=0.0215, 0.0023, and 0.0024, respectively). Vascular endothelial growth factor-C expression was also significantly correlated with CD133 expression (P=0.0002). Consequently, the 5-year survival rate of CD133-positive patients was significantly lower than that of CD133-negative patients (P=0.0002) and multivariate analysis revealed that CD133 expression was an independent prognostic factor (P=0.0103). These results suggest that CD133 expression in pancreatic cancer was significantly associated with lymphatic metastasis, VEGF-C expression, and prognosis.

Clinical significance of midkine expression in pancreatic head carcinoma.

Midkine (MK) is a heparin-binding growth factor and a product of a retinoic acid-responsive gene. Midkine is overexpressed in many carcinomas and thought to play an important role in carcinogenesis. However, no studies have been focussed on the role of MK in pancreatic carcinoma. This study sought to evaluate the clinical significance of MK expression in pancreatic head carcinoma, including the relationship between immunohistochemical expression and clinicopathologic factors such as prognosis. Immunohistochemical expression of MK and CD34 was evaluated in pancreatic head carcinoma specimens from 75 patients who underwent surgical resection. Midkine was expressed in 53.3% of patients. Midkine expression was significantly correlated with venous invasion, microvessel density, and liver metastasis (P=0.0063, 0.0025, and 0.0153, respectively). The 5-year survival rate was significantly lower for patients positive for MK vs patients negative for MK (P=0.0073). Multivariate analysis revealed that MK expression was an independent prognostic factor (P=0.0033). This is the first report of an association between MK expression and pancreatic head carcinoma. Midkine may play an important role in the progression of pancreatic head carcinoma, and evaluation of MK expression is useful for predicting malignant properties of pancreatic head carcinoma.