Department of Medicine A, University Hospital of Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.
Gerhard-Domagk-Institute for Pathology, University Hospital of Münster, Albert Schweitzer Campus 1 D17, 48149, Münster, Germany.
Cell Oncol (Dordr). 2018 Aug;41(4):455-462. doi: 10.1007/s13402-018-0382-8. Epub 2018 Jun 5.
Salivary gland cancer (SGC) is a rare and heterogeneous disease with significant differences in recurrence and metastasis characteristics. As yet, little is known about the mechanisms underlying the initiation and/or progression of these diverse tumors. In recent years, the AAA+ ATPase family members Pontin (RuvBL1, Tip49a) and Reptin (RuvBL2, Tip49b) have been implicated in various processes, including transcription regulation, chromatin remodeling and DNA damage repair, that are frequently deregulated in cancer. The aim of this study was to assess the clinical and functional significance of Reptin and Pontin expression in SGC.
Immunohistochemical staining of Pontin, Reptin, β-catenin, Cyclin D1, TP53 and MIB-1 was performed on a collection of 94 SGC tumor samples comprising 13 different histological subtypes using tissue microarrays.
We found that Reptin and Pontin were expressed in the majority of SGC samples across all histological subtypes. Patients with a high Reptin expression showed a significantly inferior 5-year overall survival rate compared to patients with a low Reptin expression (47.7% versus 78.3%; p = 0.033), whereas no such difference was observed for Pontin. A high Reptin expression strongly correlated with a high expression of the proliferation marker MIB-1 (p = 0.003), the cell cycle regulator Cyclin D1 (p = 0.006), accumulation of TP53 as a surrogate p53 mutation marker (p = 0.042) and cytoplasmic β-catenin expression (p = 0.002). Increased Pontin expression was found to significantly correlate with both cytoplasmic and nuclear β-catenin expression (p = 0.037 and p = 0.018, respectively), which is indicative for its oncogenic function.
Our results suggest a role of Reptin and Pontin in SGC tumor progression and/or patient survival. Therefore, SGC patients exhibiting a high Reptin expression may benefit from more aggressive therapeutic regimens. Future studies should clarify whether such patients may be considered for more radical surgery, extended adjuvant therapy and/or targeted therapy.
唾液腺癌（SGC）是一种罕见且异质性的疾病，其复发和转移特征存在显著差异。目前，人们对这些不同肿瘤发生和/或进展的机制知之甚少。近年来，AAA+ATP 酶家族成员 Pontin（RuvBL1，Tip49a）和 Reptin（RuvBL2，Tip49b）已被牵涉到多种过程中，包括转录调控、染色质重塑和 DNA 损伤修复，这些过程在癌症中经常失调。本研究旨在评估 SGC 中 Reptin 和 Pontin 表达的临床和功能意义。
使用组织微阵列对包含 13 种不同组织学亚型的 94 例 SGC 肿瘤样本进行了 Pontin、Reptin、β-连环蛋白、Cyclin D1、TP53 和 MIB-1 的免疫组织化学染色。
我们发现 Reptin 和 Pontin 在所有组织学亚型的大多数 SGC 样本中均有表达。与 Reptin 低表达的患者相比，Reptin 高表达的患者 5 年总生存率显著降低（47.7%对 78.3%；p=0.033），而 Pontin 则没有观察到这种差异。Reptin 高表达与增殖标志物 MIB-1（p=0.003）、细胞周期调节因子 Cyclin D1（p=0.006）、作为替代 p53 突变标志物的 TP53 积累（p=0.042）和细胞质β-连环蛋白表达（p=0.002）的高表达强烈相关。发现 Pontin 表达增加与细胞质和核β-连环蛋白表达均显著相关（p=0.037 和 p=0.018），这表明其具有致癌功能。
我们的研究结果表明 Reptin 和 Pontin 在 SGC 肿瘤进展和/或患者生存中起作用。因此，表达 Reptin 较高的 SGC 患者可能受益于更积极的治疗方案。未来的研究应阐明此类患者是否可以考虑更激进的手术、延长辅助治疗和/或靶向治疗。
