title: Prognostic significance of β2-adrenergic receptor expression in malignant melanoma.
abstract: 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.
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan. shimizuakira@gunma-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma, 371-8511, Japan. kkaira@gunma-u.ac.jp.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Kaira
authors.affiliation: Clinical Research Center, Shizuoka Cancer Center, Shizuoka, 411-8777, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Mori
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Yasuda
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Tetsunari
authors.initials: T
authors.lastname: Oyama
authors.affiliation: Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asao
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishikawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D018343:Receptors, Adrenergic, beta-2
keywords: Angiogenesis; Cutaneous; Immunohistochemistry; Melanoma; Prognostic factor; β2-Adrenergic receptor