M idkine (MK) is a heparin-binding growth factor which is the product of a retinoic acid-responsive gene whose expression increases during the early differentiation stage in embryonal carcinoma cells.(1-3) MK exhibits various activities such as vascularization, promoting the growth of fibroblast, suppressing apoptosis, and inducing cell migration, and is considered to be involved in carcinogenesis and tumor progression.(4 -9) Increased MK mRNA and protein expressions are reported in many human carcinomas such as gastric, pancreatic, bile duct, colorectal, hepatocellular, esophageal cancers, and in lung, breast, bladder, ovarian, and prostate carcinomas as well as in Wilms' tumors and neuroblastomas. (10 -20) As it is a secreted protein, MK can be detected in the blood. Increased concentrations of blood MK have been reported in esophageal cancer and neuroblastoma. (21,22) Although there are several reports indicating that serum MK (S-MK) is elevated in other cancers, those studies involved only a few subjects. (23)(24)(25) To gain a better understanding of S-MK concentrations in gastric cancer, we investigated S-MK concentrations in each group divided by the progression stage or histological type of gastric cancer.
Materials and methodsSubjects. The case subjects were patients who were newly diagnosed as having gastric cancer at one of nine hospitals in the Tokyo Metropolitan Area between 1993 and 1995. Patients who had undergone treatment for gastric cancer were excluded at entry. An endoscopy was performed on all eligible cases, and the diagnosis was confirmed by an examination of resection or biopsy specimens. Data on pathological findings, including the type and stage of the cancer, were then recorded. Gastric cancer was subdivided by progression stage (early or advanced) and histological type (intestinal or diffuse) based on the criteria proposed by the Japanese Research Society for Gastric Cancer (JRSGC). The control subjects were recruited from a group of apparently healthy people who underwent medical checkups at a health promotion center in the same area. The cases and the controls were asked to provide sera, and written informed consent was obtained from all subjects. All sera of the cases were provided within 2 months from diagnosis; and before surgery between 1993 and 1995 we enrolled 788 gastric cancer patients and 1007 apparently healthy controls. From this group, we randomly selected 275 cases considering sex and age. Between case and control subjects, sex and age (±2 years) were matched. From the control subjects with the same age and sex, one whose date of phlebotomy was the nearest to that of each case subject was selected.Serum samples of the subjects were collected using the same methods and frozen at −80°C until analysis.ELISA assay. Serum Helicobacter pylori IgG antibodies were measured by enzyme-linked immunosorbent assay (elisa) using a commercial kit (J-HM-CAP; Kyowa Medex, Japan). Intraassay coefficient of variation in J-HM-CAP (three different concentration samples in eight intra-assay...