Prognostic relevance of cathepsin D detection in micrometastatic cells in the bone marrow of patients with primary breast cancer

Abstract

Patients with an elevated level of cathepsin D in breast cancer tissue have an adverse prognosis. This study evaluated the prognostic relevance of cathepsin D detection in disseminated tumour cells in bone marrow. Bone marrow was sampled intraoperatively from both anterior iliac crests in 290 patients with primary breast cancer. Interphase cells were enhanced and stained immunocytologically with two antibodies: BM2, which detects tumour-associated glycoprotein TAG 12, which is typically expressed by almost all breast cancer cells, and the anti-cathepsin D antibody. 67 of 149 BM2-positive women (45%) developed metastatic disease (median follow-up time: 69 months). Of these, 15 were cathepsin D-positive (22%). Patients with cathepsin D-positive cells in bone marrow (n = 26; 9%) had a significantly shorter metastasis-free interval (38 months) compared with women who were cathepsin D-negative (64.5 months). The worst prognosis was seen in patients positive for both markers (30.5 months), followed by those who were cathepsin D-negative and BM2-positive (48 months). The detection of cathepsin D on disseminated tumour cells characterises a subgroup of patients with a poorer prognosis who should undergo more aggressive adjuvant systemic therapy.

Multidisciplinary breast centres in Germany: a review and update of quality assurance through benchmarking and certification

“…Thus, local tumour control has been integrated into multimodal systemic treatment strategies based on a definitive diagnosis by, e.g. diagnostic sentinel lymph node biopsy [46, 47] or the detection of disseminated tumour cells [48, 49]. …”

The Role and Clinical Relevance of Disseminated Tumor Cells in Breast Cancer

“…It supports also the theory of cancer cell dormancy; this hypothesis holds that isolated tumor cells at secondary sites are able survive in a quiescent state, either withdrawing completely from the cell cycle or persisting at a slow proliferation rate counterbalanced by apoptosis [32]. Furthermore, the surface of DTCs is characterized by reduced expression of MHC class I molecules, which could result in an immune escape of these cells [33], as well as high activity of tumor invasiveness markers, such as urokinase plasminogen activator (uPA) and its membrane receptor (uPA-R), extracellular matrix metalloproteinase inducer (EMMPRIN) or cathepsin B, which enables destruction of basement membrane and stromal invasion [34,35,36,37]. Elevated expression of cell adhesion molecule E-cadherin on DTCs might be involved in the process of forming a metastasis [38].…”

Zertifizierte multidisziplinäre Brustzentren

“…So erfolgte die Integration der lokalen Tumorkontrolle in multimodale systemische Therapiekonzepte entsprechend einer differenzierten Indikationsstellung z. B. durch die Sentinel-Lymphknoten-Diagnostik [10,24] und durch Nachweis der Tumorzelldissemination [31,34].…”