Pretreatment serum syndecan-1 levels and outcome in small cell lung cancer patients treated with platinum-based chemotherapy

Anttonen, Anu; Leppä, Sirpa; Ruotsalainen, Tarja; Alfthan, Henrik; Mattson, Karin; Joensuu, Heikki

doi:10.1016/S0169-5002(03)00196-X

Next »Lung Cancer
Volume 41, Issue 2 , Pages 171-177, August 2003

Pretreatment serum syndecan-1 levels and outcome in small cell lung cancer patients treated with platinum-based chemotherapy

Anu Anttonen
- Department of Oncology, Helsinki University Central Hospital, P.O. Box 180, FIN-00029 Helsinki, Finland
- Corresponding author. Tel.: +358-9-4711; fax: +358-9-471-74202
Sirpa Leppä
- Department of Oncology, Helsinki University Central Hospital, P.O. Box 180, FIN-00029 Helsinki, Finland
- Molecular Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, FIN-00029 Helsinki, Finland
Tarja Ruotsalainen
- Department of Oncology, Helsinki University Central Hospital, P.O. Box 180, FIN-00029 Helsinki, Finland
Henrik Alfthan
- Clinical Chemistry, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00029 Helsinki, Finland
Karin Mattson
- Department of Medicine, Division of Pulmonary Medicine, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00029 Helsinki, Finland
Heikki Joensuu
- Department of Oncology, Helsinki University Central Hospital, P.O. Box 180, FIN-00029 Helsinki, Finland
- Molecular Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, FIN-00029 Helsinki, Finland

Received 22 October 2002; received in revised form 13 March 2003; accepted 14 March 2003.

Abstract

Syndecan-1 is a multifunctional transmembrane heparan sulphate proteoglycan (HSPG) that is present on a variety of cell types. The extracellular syndecan domains can be shed from the cell surface in a highly regulated process called ectodomain shedding. We studied the influence of soluble syndecan-1 on outcome in 88 small cell lung cancer (SCLC) patients treated within the context of two randomised clinical trials with platinum-based therapy. Serum syndecan-1 concentrations were determined using enzyme-linked immunosorbent assay (ELISA) from sera taken prior to initiation of chemotherapy. Patients with the serum syndecan-1 level within the highest tertile (>212 μg/l) had only 38% 1-year and 3% 2-year survival, whereas 58% of those with a lower serum level survived for 1 year and 25% for 2 years following the diagnosis (P=0.0034). A high serum syndecan-1 level (>212 μg/l) was associated with a high pretreatment lactate dehydrogenase (LDH) level (P=0.0024) and a poor Karnofsky's performance status (P=0.021), but not with the clinical stage or the presence of distant metastases at diagnosis. A high serum syndecan-1 level had independent influence on survival also in a multivariate analysis (the relative risk, RR, 1.68; 95% CI, 1.02–2.77; P=0.044) together with the clinical stage (RR, 1.72; 95% CI, 1.05–2.82; P=0.032). We conclude that high pretreatment serum syndecan-1 level is associated with poor prognosis in SCLC treated with platinum-based chemotherapy.

Keywords: Lung cancer, Syndecan, Prognosis, Cisplatin, Carboplatin