title: ADAM28 is a serological and histochemical marker for non-small-cell lung cancers.
abstract: ADAM28 (a disintegrin and metalloproteinase 28) is over-expressed in non-small-cell lung cancer (NSCLC) with correlation to cancer cell proliferation, tumor size and lymph node metastasis. The present study was aimed to develop an enzyme-linked immunosorbent assay (ELISA) system for diagnosis and monitoring of NSCLC. Our ELISA specifically measured ADAM28, showing negligible cross-reactivity with other metalloproteinases. The ADAM28 level in the NSCLC tissue was remarkably 36.9-fold higher than that in the non-neoplastic lung tissue (p < 0.001). The serum level was significantly 4.6-fold higher in the NSCLC patients (5.41 +/- 8.62 ng/ml; n = 102) than in the control subjects (1.17 +/- 0.93 ng/ml; n = 20) (p < 0.001), and increased with progress of tumor stage (p < 0.001). The level was also significantly higher in the patients with recurrent carcinoma than the control (p < 0.001) and in the patients with lymph node metastasis than those without metastasis (p < 0.001). The sensitivity, false-negative rate and AUC for ADAM28 were better than those for carcinoembryonic antigen. The combination of both assays improved the sensitivity, specificity, false-positive and false-negative rates for NSCLC. There was a positive correlation between the ADAM28 level measured by ELISA system and the degree of immunostaining in the lung adenocarcinomas with a size of <or=20 mm in diameter. The adenocarcinoma patients showing the high immunohistochemical reaction exhibited a poorer disease-free survival than those with the lower immunoreactivity (n = 102; p < 0.05). These data demonstrate that our ELISA is specific and sensitive to monitor the levels of ADAM28 in the samples from NSCLC patients and suggest that ADAM28 is a useful serological and histochemical marker for NSCLC.
authors.affiliation: Department of Pathology, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kuroda
authors.forename: Satsuki
authors.initials: S
authors.lastname: Mochizuki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shimoda
authors.forename: Miyuki
authors.initials: M
authors.lastname: Chijiiwa
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kamiya
authors.forename: Yotaro
authors.initials: Y
authors.lastname: Izumi
authors.forename: Masazumi
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Horinouchi
authors.forename: Masahumi
authors.initials: M
authors.lastname: Kawamura
authors.forename: Koichi
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000230:Adenocarcinoma / Q000097:blood* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D018287:Carcinoma, Large Cell / Q000097:blood* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000473:pathology; D011379:Prognosis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D051722:ADAM Proteins; C410224:ADAM28 protein, human