Evaluation of ADAM28 as a serological and histochemical marker for non-small cell lung cancers.

Abstract

10599 Background: ADAMs (a disintegrin and metalloproteinases) are a gene family, which exhibit both proteolytic and adhesive properties. ADAM28 is over-expressed in non-small cell lung cancer (NSCLC) with correlation to cancer cell proliferation, tumor size and lymph node metastasis. This study was aimed to develop an enzyme-linked immunosorbent assay (ELISA) system for serological and histochemical marker of NSCLC. Methods: AnELISA system by using two monoclonal antibodies against ADAM28. Serum levels of ADAM28 in 102 NSCLC and 20 controls were measured. ADAM28 was also examined in urine samples. ADAM28 production levels in the resected specimens were compared with the degree of immunoreactivity. The patients were classified to three groups (high-, middle- and the low-expressing) according to the immunostaining and analyzed by the Kaplan-Meier. Results: 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 NSCLC patients (5.41 ± 8.62 ng/mL) than in controls (1.17 ± 0.93 ng/mL) (p < 0.001), and increased with progress of stage. The level was also significantly higher in the patients with recurrence than controls (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 CEA. The detection rate in urine was increased with progress of stage, and significant correlated with serum subjects (n = 45; p < 0.001). There was a positive correlation between the ADAM28 level and the degree of immunostaining in the lung adenocarcinomas with a size of ≤ 20 mm in diameter. The patients showing the high immunohistochemical reaction exhibited a poorer disease-free survival (n = 102; p < 0.05). Conclusions: Our data demonstrate that our ELISA is specific and sensitive to monitor the levels of ADAM28 in NSCLC and suggest that ADAM28 is a useful serological and histochemical marker for NSCLC. No significant financial relationships to disclose.