Clinical & Experimental Metastasis

, Volume 24, Issue 7, pp 567–574 | Cite as

Serum angiogenin levels predict treatment response in patients with stage IV melanoma

  • Pia Vihinen
  • Minna Kallioinen
  • Meri-Sisko Vuoristo
  • Johanna Ivaska
  • Kari J. Syrjänen
  • Marjo Hahka-Kemppinen
  • Pirkko-Liisa Kellokumpu-Lehtinen
  • Seppo O. Pyrhönen
Research Paper


This work was conducted to find out new potential serum markers and study their role as predictive factors in patients with metastatic melanoma. Serum samples from 68 patients with stage IV malignant melanoma were collected just before current treatment and screened for 79 different cytokines by using a multi-cytokine array. Angiogenin, which is a protein capable of promoting angiogenesis, was found to be markedly elevated among a sub-group of patients with progressive disease (PD) and thus was subjected to further analysis. The mean serum angiogenin level was 270 ng/ml and the median 236 ng/ml (STD 163 ng/ml). Concentrations were significantly higher among men than in women (P = 0.031), whereas patient’s age, site of the primary tumour, Clark’s or Breslow’s classifications were not associated with angiogenin levels. Patients with only lymph node metastases had markedly lower angiogenin levels than those with metastases at other sites (P = 0.05). High angiogenin levels were significantly (P = 0.015; Kruskal–Wallis) associated with poor treatment response with chemoimmunotherapy. Treatment-related survival (TRS) was shorter (10 months) in patients with above-median values than in those with below-median levels (19 months, P = NS). Cox multivariate regression model was used to control for the confounding by the classical prognostic factors of melanoma (age, sex, disease burden, performance score, site of metastases). Disease burden was the only variable that remained in the model as a significant independent predictor of TRS (P = 0.044). These data suggest that serum angiogenin levels might be of predictive value in the evaluation of treatment response for patients with stage IV melanoma.


Angiogenin Cytokine array Melanoma Prognosis Survival 



Analysis of variance


Dacarbazine, vincristine, bleomycin, lomustine


Complete response


Cytoplasmic melanoma-associated antigen


Basic fibroblast growth factor


Hazard ratio






Lactate dehydrogenase




Likelihood ratio


Melanoma antigen recognized by T cells


Melanoma inhibitory activity


Matrix metalloproteinase




Progressive disease


Platelet derived growth factor


Partial response


Odds ratio


Overall survival


Stable disease


Standard deviation


Tumour-associated macrophage


Treatment related survival


Vascular endothelial growth factor


Vinorelbine, carboplatin, interleukin-2



This study has been supported by the research grants from the Finnish Cancer Foundation, Turku University Hospital Foundation and Pirkanmaa Hospital District Research Fund.


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Copyright information

© Springer Science + Business Media B.V. 2007

Authors and Affiliations

  • Pia Vihinen
    • 1
  • Minna Kallioinen
    • 1
  • Meri-Sisko Vuoristo
    • 2
  • Johanna Ivaska
    • 3
  • Kari J. Syrjänen
    • 1
  • Marjo Hahka-Kemppinen
    • 4
  • Pirkko-Liisa Kellokumpu-Lehtinen
    • 2
  • Seppo O. Pyrhönen
    • 1
  1. 1.Department of Oncology and RadiotherapyTurku University HospitalTurkuFinland
  2. 2.Department of OncologyTampere University HospitalTampereFinland
  3. 3.VTT Technical Research Centre for Finland, Medical BiotechnologyTurkuFinland
  4. 4.Department of OncologyHelsinki University HospitalHelsinkiFinland

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