Die Überexpression von Matrix Metalloproteinase 2 (MMP-2) ist mit einer Frühdisseminierung bei operablem Adenokarzinom der Lunge assoziiert

Abstract

The present study was performed to investigate the impact of MMP-2 expression on dissemination of individual tumor cells in non-small cell lung cancer. Primary tumors of 189 consecutive patients with completely resected non-small cell lung cancer were examined for MMP-2 expression by immunohis to chemistry. Homogeneous immunostaining of cancer cells was considered positive and heterogeneous or no staining was considered negative concerning overexpression of MMP-2. Regional lymph nodes of 102 patients were collected intraoperatively. In 78 of these patients, preoperatively obtained bone marrow samples were available. Cryostat sections of lymph nodes which were assessed as tumor-free in a preceding conventional histopathological screening were examined for disseminated individual tumor cells by immunohistochemical staining using the monoclonal antiepithelial antibody Ber-EP4. Individual tumor cells in bone marrow cytospins were detected immunocytochemically using a monoclonal anti human cytokeratin No. 18 (CK18) antibody. Overexpression of MMP-2 was observed in 64 (33.9%) patients and did not correlate with clinicopathological parameters. In patients without lymph node involvement (pNo) MMP-2 overexpression was an independent prognostic parameter for unfavorable outcome. Log rank analysis showed a significant association of MMP-2 overexpression with shortened cancer-related survival (p = 0.04). A significant correlation between MMP-2 overexpression and disseminated tumor cells in lymph nodes (p = 0.02) or bone marrow (p = 0.04) was observed in adenocarcinomas of the lung. The present study revealed that MMP-2 overexpression predicts a poor prognosis in early stage non-small cell lung cancer and correlates with dissemination of individual tumor cells in adenocarcinoma of the lung. Therefore it might be worth to investigate the role of MMP inhibitors as adjuvant therapeutic agents in non-small cell lung cancer.