Tumor Biology

, Volume 37, Issue 5, pp 5971–5978 | Cite as

Prognostic significance of β2-adrenergic receptor expression in malignant melanoma

  • Akira Shimizu
  • Kyoichi Kaira
  • Keita Mori
  • Madoka Kato
  • Kimihiro Shimizu
  • Masahito Yasuda
  • Ayumi Takahashi
  • Tetsunari Oyama
  • Takayuki Asao
  • Osamu Ishikawa
Original Article


Recent studies cite β2-adrenergic receptor (β2AR) antagonists as novel therapeutic agents for melanoma, as they may reduce the disease progression. The β2AR has shown to be expressed in malignant melanoma. However, it remains unclear whether the β2AR expression has a clinical and pathological significance in patients with cutaneous malignant melanoma. We herein conducted a clinicopathological study to investigate the protein expression of β2AR in malignant melanoma of the skin and its prognostic significance. One hundred thirty-three patients with surgically resected cutaneous malignant melanoma were evaluated. Tumor sections were stained by immunohistochemistry for β2AR, Ki-67, the microvessel density (MVD) determined by CD34, and p53. β2AR was highly expressed in 44.4 % (59 out of 133) of the patients. The expression of β2AR was significantly associated with the tumor thickness, ulceration, T factor, N factor, disease stage, tumor size, cell proliferation (Ki-67), and MVD (CD34). Using Spearman’s rank test, the β2AR expression was correlated with Ki-67 (r = 0.278; 95 % CI, 0.108 to 0.432; P = 0.001), CD34 (r = 0.445; 95 %CI, 0.293 to 0.575; P < 0.001), and the tumor size (r = 0.226; 95 % CI, 0.053 to 0.386; P = 0.008). Using a univariate analysis, the tumor thickness, ulceration, disease stage, β2AR, Ki-67, and CD34 had a significant relationship with the overall and progression-free survivals. A multivariable analysis confirmed that β2AR was an independent prognostic factor for predicting a poor overall survival (HR 1.730; 95 % CI 1.221–2.515) and progression-free survival (HR 1.576; 95 % CI 1.176–2.143) of malignant melanoma of the skin. β2AR can serve as a promising prognostic factor for predicting a worse outcome after surgical treatment and may play an important role in the development and aggressiveness of malignant melanoma.


Melanoma β2-Adrenergic receptor Prognostic factor Cutaneous Immunohistochemistry Angiogenesis 



We appreciate Ms. Yuka Matsui for her technical assistance regarding the submitted manuscript and Ms. Tomoko Okada for her help with the data collection and technical assistance. We would also like to sincerely thank Prof. Masahiko Nishiyama of Department of Molecular Pharmacology and Oncology, Gunma University Graduate School of Medicine, for his critical review of this manuscript.

Compliance with ethical standards

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Akira Shimizu
    • 1
  • Kyoichi Kaira
    • 2
  • Keita Mori
    • 5
  • Madoka Kato
    • 1
  • Kimihiro Shimizu
    • 3
  • Masahito Yasuda
    • 1
  • Ayumi Takahashi
    • 1
  • Tetsunari Oyama
    • 4
  • Takayuki Asao
    • 2
  • Osamu Ishikawa
    • 1
  1. 1.Department of DermatologyGunma University Graduate School of MedicineMaebashiJapan
  2. 2.Department of Oncology Clinical DevelopmentGunma University Graduate School of MedicineMaebashiJapan
  3. 3.Department of Thoracic and Visceral Organ SurgeryGunma University Graduate School of MedicineMaebashiJapan
  4. 4.Department of Diagnostic PathologyGunma University Graduate School of MedicineMaebashiJapan
  5. 5.Clinical Research Center, Shizuoka Cancer CenterShizuokaJapan

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