Oral Presentation 6th Australian Health and Medical Research Congress 2012

Circulating N-cadherin levels are a negative prognostic indicator in patients with multiple myeloma (#161)

Andrew Zannettino 1 , Kate Vandyke 1 , Annie Chow 2 , Sharon Williams 1 , Luen B To 2
  1. University of Adelaide, Adelaide, SA, Australia
  2. Haematology, SA Pathology, Adelaide, SA, Australia

N-cadherin is a transmembrane or secreted homophilic adhesion molecule that regulates blood vessel morphogenesis and osteoblastogenesis in adult tissues. Increased expression of N-cadherin is associated with disease progression and poor prognosis in epithelial cancers including breast cancer. Here we investigated the prognostic significance of upregulated N-cadherin expression in multiple myeloma (MM). N-cadherin was measured in the peripheral blood of 84 patients with newly-diagnosed symptomatic MM, 27 patients with monoclonal gammopathy of undetermined significance (MGUS) and 27 age-matched controls. In addition, N-cadherin gene and protein expression was assessed in iliac crest trephine biopsies and CD38++/CD138+ plasma cells from MM and MGUS patients or haematologically normal donors. Our results indicate that N-cadherin protein and gene expression is abnormally increased in MM patient bone marrow plasma cells. In addition, we found that the levels of circulating N-cadherin were elevated in a subset of MM (mean: 14.50 ng/mL, range: 0 – 146.78 ng/mL) and MGUS patients (mean: 5.07 ng/mL, range: 0 – 29.87 ng/mL), relative to normal controls (mean: 2.66 ng/mL, range: 0 – 5.96 ng/mL). Notably, patients with abnormally high levels of N-cadherin (> 6 ng/mL) have decreased progression-free survival (p = 0.036; hazard ratio: 1.94) and overall survival (p = 0.002; hazard ratio: 3.15), when compared with patients with normal N-cadherin levels (≤ 6 ng/mL). Furthermore, stratification of patients by N-cadherin and ISS, identified a sub-group of ISS III patients with high N-cadherin levels who did significantly worse than the other groups. Collectively, our studies demonstrate that circulating N-cadherin levels are potentially a viable prognostic marker for high risk MM patients.