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. 2007 Aug 6;97(3):405-11.
doi: 10.1038/sj.bjc.6603879. Epub 2007 Jul 10.

Clinical significance of midkine expression in pancreatic head carcinoma

S Maeda  1 , H Shinchi, H Kurahara, Y Mataki, H Noma, K Maemura, K Aridome, T Yokomine, S Natsugoe, T Aikou, S Takao
Affiliations

Clinical significance of midkine expression in pancreatic head carcinoma

S Maeda et al. Br J Cancer. .

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=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.

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Figures

Figure 1
Figure 1
Immunohistochemical staining for MK in invasive ductal adenocarcinoma of the pancreas head. (A) Normal pancreatic ductal epithelium dissected approximately 3 cm apart from the cancerous region (× 200). Note that almost all cells are unstained or stained very slightly by the antibody. (B) Carcinoma cells positively stained by MK antibody (× 400). Note cytoplasmic staining for MK. (C) Carcinoma cells stained negatively by MK antibody (× 400).
Figure 2
Figure 2
Western blotting for MK protein. (A) Pancreatic primary tumours (PT) and non-cancerous regions (N) dissected approximately 3 cm apart from the cancerous region. Cases 1 and 2 are from each independent patient. (B) Pancreatic carcinoma cell lines. Note the presence of a 13-kDa band corresponding to MK protein in primary tumours and cultured cells. The presence of a 43-kDa band corresponding to β-actin protein in each sample indicates that samples are equally loaded.
Figure 3
Figure 3
Immunohistochemical staining for CD34 protein in invasive ductal adenocarcinoma of the pancreas head. (A) A microphotograph of pancreatic head carcinoma stained by CD34 antibody and judged as high-grade MVD⩾40 (× 200). (B) A microphotograph of pancreatic head carcinoma stained by CD34 antibody and judged as low-grade MVD<40 (× 200).
Figure 4
Figure 4
Microvessel density (MVD) evaluated by CD34 staining and subsequent observation (0.785 mm2 per field) under a microscope with × 200 power. The MVD (mean±s.d.=45.72±10.77) in MK-positive tumours was significantly higher than that (36.69±11.91) in MK-negative tumours (P=0.0025).
Figure 5
Figure 5
Comparison of survival curves (depicted according to the Kaplan–Meier method) of patients with pancreatic head carcinomas in relation to MK expression. The 5-year survival rate was 0.0% for patients with MK-positive tumours and 19.3% for patients with MK-negative tumours, which is significantly different (P=0.0073).
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