Hakata Yuko, Fukui Hirokazu, Sekikawa Akira, Yamagishi Hidetsugu, Ichikawa Kazuhito, Tomita Shigeki, Imura Johji, Kawamata Hitoshi, Imai Yutaka, Fujimori Takahiro
Departments of Surgical and Molecular Pathology, and ; Oral Surgery, Dokkyo University School of Medicine, Tochigi 321-0293, Japan.
Exp Ther Med. 2010 May;1(3):437-443. doi: 10.3892/etm_00000068. Epub 2010 May 1.
β-catenin and its target gene products have been thought to play pivotal roles in the progression of various neoplasias. In the present study, we examined the expression of β-catenin and regenerating gene (REG) Iα in salivary gland tumors and investigated its relationship to their cell proliferative ability. Nineteen patients with pleomorphic adenoma (PA) and 17 patients with malignant salivary gland tumors, including 7 adenoid cystic carcinomas, 7 mucoepidermoid carcinomas and 3 polymorphous low-grade adenocarcinomas, were enrolled. The specimens that had been surgically resected from these patients were examined using immunohistochemistry for β-catenin, REG Iα and Ki67. The relationships between clinicopathological features and β-catenin or REG Iα expression were then analyzed. β-catenin immunoreactivity was positive in 14 PAs (73.3%) and 14 malignant salivary gland tumors (82.4%). Four (28.6%) of the 14 β-catenin-positive PAs showed clear β-catenin immunoreactivity at the plasma membrane (membrane type), while 10 (71.4%) showed diffuse immunoreactivity in the cytoplasm and nucleus but not at the plasma membrane (non-membrane type). Twelve (85.9%) of the 14 malignant salivary gland tumors showed non-membrane-type β-catenin expression. Six (31.6%) of the 19 PAs and 10 (58.8%) of the 17 malignant salivary gland tumors were positive for REG Iα expression. PAs with non-membrane-type β-catenin expression showed a significantly higher Ki67 labeling index than PAs with negative or membrane-type expression. Additionally, PAs that were REG Iα-positive showed a significantly higher Ki67 labeling index than those that were negative. Non-membrane-type β-catenin expression was related to REG Iα positivity in PA lesions. β-catenin and its associated REG Iα protein may play a role as growth-promoting factors in the development of salivary gland tumors.
β-连环蛋白及其靶基因产物被认为在各种肿瘤的进展中起关键作用。在本研究中，我们检测了涎腺肿瘤中β-连环蛋白和再生基因（REG）Iα的表达，并研究了其与细胞增殖能力的关系。纳入了19例多形性腺瘤（PA）患者和17例涎腺恶性肿瘤患者，其中包括7例腺样囊性癌、7例黏液表皮样癌和3例多形性低度腺癌。对这些患者手术切除的标本进行免疫组织化学检测，以检测β-连环蛋白、REG Iα和Ki67。然后分析临床病理特征与β-连环蛋白或REG Iα表达之间的关系。β-连环蛋白免疫反应性在14例PA（73.3%）和14例涎腺恶性肿瘤（82.4%）中呈阳性。14例β-连环蛋白阳性的PA中有4例（28.6%）在质膜处显示清晰的β-连环蛋白免疫反应性（膜型），而10例（71.4%）在细胞质和细胞核中显示弥漫性免疫反应性，但在质膜处未显示（非膜型）。14例涎腺恶性肿瘤中有12例（85.9%）显示非膜型β-连环蛋白表达。19例PA中有6例（31.6%）和17例涎腺恶性肿瘤中有10例（58.8%）REG Iα表达呈阳性。非膜型β-连环蛋白表达的PA显示出比阴性或膜型表达PA显著更高的Ki67标记指数。此外，REG Iα阳性的PA显示出比阴性PA显著更高的Ki67标记指数。非膜型β-连环蛋白表达与PA病变中的REG Iα阳性相关。β-连环蛋白及其相关的REG Iα蛋白可能在涎腺肿瘤的发生发展中作为生长促进因子发挥作用。
