Syndecan‑1 expression is an independent favourable prognostic marker in oesophageal adenocarcinoma and represents a potential therapeutic target

Duygu Akca; Adrian Simon; Reinhard Buettner; Christiane Bruns; Wolfgang Schroeder; Thomas Zander; Florian Gebauer; Alexander Quaas

doi:10.3892/ol.2023.13942

Syndecan‑1 expression is an independent favourable prognostic marker in oesophageal adenocarcinoma and represents a potential therapeutic target

Oncol Lett. 2023 Jul 4;26(2):356. doi: 10.3892/ol.2023.13942. eCollection 2023 Aug.

Authors

Duygu Akca¹, Adrian Simon², Reinhard Buettner², Christiane Bruns³, Wolfgang Schroeder³, Thomas Zander⁴, Florian Gebauer³, Alexander Quaas²

Affiliations

¹ Department of Pathology, Tekirdag Dr. Ismail Fehmi Cumalioglu City Hospital, 59030 Tekirdag, Turkey.
² Institute of Pathology, University of Cologne, Faculty of Medicine and University Hospital Cologne, D-50937 Cologne, Germany.
³ Department of General, University of Cologne, Faculty of Medicine and University Hospital Cologne, D-50937 Cologne, Germany.
⁴ Department I of Internal Medicine, Center for Integrated Oncology, University of Cologne, Faculty of Medicine and University Hospital Cologne, D-50937 Cologne, Germany.

Abstract

Because of the poor prognosis of oesophageal adenocarcinoma (EAC), there is an urgent need for additional therapeutic approaches. Syndecan-1 (CD138) is a cell-surface heparan sulphate that is overexpressed in multiple myeloma cells and several carcinomas. Specific drugs targeting CD138 [e.g. antibody-linked drug conjugates (ADCs)] are currently being assessed; however, the significance and implication of CD138 expression in EAC is mostly unknown. In the present study, CD138 expression was assessed using immunohistochemistry, and its association with histopathological parameters and ERBB2 (Her2/neu) amplification status in patients treated with primary resection and neoadjuvant (radio-)chemotherapy was investigated. Of the 723 cases of EAC included, 232 tumours (32.1%) expressed CD138, with 96 tumours displaying strong expression (13.3%). Patients with CD138-positive tumours had less invasive carcinoma, fewer lymph mode metastases and a significantly longer overall survival (OS) than patients with CD138-negative tumours (P=0.002). In multivariate analysis, strong CD138 expression was an independent favourable prognostic factor (P=0.02). Patients who received neoadjuvant CROSS (carboplatin, paclitaxel and intensity modulated radiotherapy) therapy and had CD138-positive tumours lived significantly longer (P=0.04). In tumours without Her2/neu amplification, CD138 expression was associated with a longer OS (P=0.02). In conclusion, CD138 in cancer is already used as a target for ADCs, such as indatuximab ravtansine, the effectiveness of which depends on the extent of CD138 on tumour cells. This indicates that CD138 is also a predictive, therapeutically relevant biomarker. Regardless of the favourable prognostic effect of CD138 in EAC, there is an urgent clinical need for personalized therapeutics in relapse. Future clinical trials now need to show how effective the corresponding ADCs are in CD138-positive EACs.

Keywords: BT062; SDC1; antibody-linked drug conjugate; indatuximab ravtansine; oesophageal cancer; targeted therapies.

Grants and funding

Funding: No funding was received.