Clinical significance of midkine expression in pancreatic head carcinoma

Abstract

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 ¼ 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 ¼ 0.0073). Multivariate analysis revealed that MK expression was an independent prognostic factor (P ¼ 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.

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

“…The presence of VEGF-C and CXCR4 immunoreactivity in over 10% of tumour cells was defined as positive expression. Immunostaining for CD34 was assessed to determine microvessel density (MVD) (Weidner et al, 1991;Maeda et al, 2007;Mohammed et al, 2007). Vessels in the five most highly visualised areas (0.785 mm 2 per field) by CD34 immunostaining were counted under a  200 light microscope.…”

“…This could be because of the propensity for early metastasis to regional lymph nodes and the liver, as the presence or absence of lymph node metastasis is an important prognostic factor for patients with pancreatic cancer (Maeda et al, 2007).…”

Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions

“…MDK shows highly increased expression in a number of malignant tumors (Nakagawara et al, 1995;O'Brien et al, 1996;Mishima et al, 1997;Ye et al, 1999;Ikematsu et al, 2000;Jia et al, 2007;Maeda et al, 2007) and enhances tumor progression by promoting survival, growth, migration and angiogenic activity Takei et al, 2001;Kadomatsu and Muramatsu, 2004;Mirkin et al, 2005;Tong et al, 2007). In human brain tumors, especially MDK is overexpressed during tumor progression, and patients whose tumors express a higher level of MDK have a worse prognosis (Mishima et al, 1997).…”

The Signal Peptide of the Tumor-shared Antigen Midkine Hosts CD4+ T Cell Epitopes

“…In tumors, MDK exhibits angiogenic (11), mitogenic (12), and antiapoptotic activities (13). Its expression in tumors (8,14) and its concentration in plasma (15) are associated with a poor disease outcome. Its various functions and expression in many tumors led us to investigate whether MDK can induce cellular cytotoxic responses in humans (16).…”