Epigenetic inactivation of galanin receptors in salivary duct carcinoma of the parotid gland: Potential utility as biomarkers for prognosis

Kanazawa,Takeharu; Misawa,Kiyoshi; Fukushima,Hirofumi; Misawa,Yuki; Sato,Yukiko; Maruta,Mikiko; Imayoshi,Shoichiro; Kusaka,Gen; Kawabata,Kazuyoshi; Mineta,Hiroyuki; Carey,Thomas  E.; Nishino,Hiroshi

doi:10.3892/ol.2018.8525

Epigenetic inactivation of galanin receptors in salivary duct carcinoma of the parotid gland: Potential utility as biomarkers for prognosis

Authors:
- Takeharu Kanazawa
- Kiyoshi Misawa
- Hirofumi Fukushima
- Yuki Misawa
- Yukiko Sato
- Mikiko Maruta
- Shoichiro Imayoshi
- Gen Kusaka
- Kazuyoshi Kawabata
- Hiroyuki Mineta
- Thomas E. Carey
- Hiroshi Nishino
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Affiliations: Department of Otolaryngology/Head and Neck Surgery, Jichi Medical University, Shimotsuke, Tochigi 329‑0498, Japan, Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu 431‑3192, Japan, Division of Head and Neck, Cancer Institute, Japanese Foundation of Cancer Research, Tokyo 135‑8550, Japan, Department of Pathology, Cancer Institute, Japanese Foundation of Cancer Research, Tokyo 135‑8550, Japan, Department of Otolaryngology/Head and Neck Surgery, Jichi Medical University, Saitama Medical Center, Saitama 330‑8503, Japan, Department of Neurosurgery, Jichi Medical University, Saitama Medical Center, Saitama 330‑8503, Japan, Laboratory of Head and Neck Cancer Biology, Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109, USA
Published online on: April 18, 2018 https://doi.org/10.3892/ol.2018.8525
Pages: 9043-9050
Copyright: © Kanazawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Salivary duct carcinoma (SDC) constitutes one of the most aggressive cancers in the salivary gland and is associated with a poor prognosis; however, no established systemic therapy options are available. SDC exhibits biological similarity to prostate and breast cancers, therefore anti‑hormone therapy and molecular target therapies are available, however with limited beneficial effects. Galanin and galanin receptors (GALRs) are well established as molecular biomarkers to predict the survival rate and risk of recurrence of head and neck squamous cell carcinoma. The present study investigated the clinicopathological features of patients with SDC and the methylation status of their galanin and GALR genes to demonstrate the prognostic value for this disease. The median overall survival (OS) was 37.2 months. T‑stage, N‑stage, disease stage, tumor size, and preoperative facial paralysis were significantly associated with OS, whereas human epidermal growth factor receptor 2 (HER2) overexpression was not. GALR1 and GALR2 methylation rates in tumor tissues were significantly increased compared with normal tissues with 9.85‑ and 4.49‑fold increase, respectively. p27kip1 and p57kip2 expression significantly inversely correlated with the methylation rate of GALR1 and GALR2. In addition, the observed GALR1 and/or GALR2 methylation rates were significantly correlated with a decrease in OS. These results suggest that GALR1 and GALR2 may serve as potential prognostic factors and therapeutic targets in SDC.

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