Involvement of Adrenomedullin Expression in Tumor Cells and Stroma in the Development of Diabetes in Pancreatic Cancer Patients

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  • IMAI Hideyuki
    Department of Pathology and Laboratory Medicine, Showa University School of Medicine Department of Pathology and Laboratory Medicine, Showa University Fujigaoka Hospital Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Showa University Fujigaoka Hospital
  • OHIKE Nobuyuki
    Department of Pathology and Laboratory Medicine, Showa University Fujigaoka Hospital
  • NOROSE Tomoko
    Department of Pathology and Laboratory Medicine, Showa University Fujigaoka Hospital
  • ISOBE Tomohide
    Department of Pathology and Laboratory Medicine, Showa University Fujigaoka Hospital
  • FUJIMASA Koichiro
    Department of Pathology and Laboratory Medicine, Showa University School of Medicine Department of Pathology and Laboratory Medicine, Showa University Fujigaoka Hospital
  • NAGAHAMA Masatsugu
    Department of Medicine, Division of Gastroenterology, Showa University Fujigaoka Hospital
  • TANAKA Jun-ichi
    Department of Surgery, Division of General and Gastroenterological Surgery, Showa University Fujigaoka Hospital
  • NAGASAKA Shoichiro
    Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Showa University Fujigaoka Hospital
  • TAKIMOTO Masafumi
    Department of Pathology and Laboratory Medicine, Showa University School of Medicine

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Some studies have reported that adrenomedullin （AM） is involved in diabetes mellitus （DM） associated with pancreatic cancer. Therefore, in this study we investigated the relationship between diabetes and AM expression in patients with pancreatic cancer. We examined 48 biopsies and 26 surgical resections from 74 patients with histologically diagnosed pancreatic cancer. Patients were classified into either DM or non-DM groups. The immunohistochemical expression of AM and various clinicopathological factors were compared between the two groups. Among the biopsy cases, 21 were classified as DM and 27 as non-DM. AM expression in pancreatic cancer cells was significantly lower in the DM group （p＝0.03）. No significant differences were noted in age, body mass index, tumor diameter or location, serum CA19-9, amylase, or C-reactive protein levels, pancreatic ductal dilatation, portal vein invasion, clinical stage, or histological differentiation between the DM and non-DM groups. The proportion of men was significantly lower in the DM group （p＝0.04）, as was the frequency of liver metastasis at diagnosis （p＝0.03）. Among the resection cases, 13 were classified as DM and 13 as non-DM. There were no significant differences in AM expression in pancreatic cancer cells between the two groups. However, marked AM expression was observed in the inflammatory cells and fibroblasts of the tumor stroma in all cases. In addition, the inflammatory response in the tumor stroma tended to be stronger in the DM group. Although the present study failed to find a positive correlation between diabetes and AM expression in pancreatic cancer cells, the results indicate that AM expression in stromal cells may be more closely related to the development of DM in pancreatic cancer patients.

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