Nikitakis Nikolaos G, Scheper Mark A, Papanikolaou Vasileios S, Sklavounou Alexandra, Sauk John J
Department of Oral Pathology and Medicine, School of Dentistry, National and Kapodistrian University of Athens, Athens, Greece.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Jun;107(6):837-43. doi: 10.1016/j.tripleo.2008.12.052. Epub 2009 Mar 9.
Signal transducer and activator of transcription 3 (Stat3) and survivin have been shown to exert oncogenic effects in various human neoplasms. The purpose of this study was to evaluate the expression of tyrosine phosphorylated (active) Stat3 and survivin in various benign and malignant salivary gland tumors (SGTs).
Eighty-six SGTs (65 malignant and 21 benign tumors of various histopathologic subtypes) were immunohistochemically stained with antisurvivin or anti-phosphorylated tyrosine-705 (p-tyr) Stat3 antibodies. Immunohistochemical reactivity was graded in a semiquantitative manner; a combined score of immunohistochemical positivity (0-6) was calculated for each tumor by adding the individual scores for percentage of tumor cells (0-3) and intensity of staining (0-3).
Survivin was immunohistochemically detected in all studied benign and malignant SGTs; p-tyr Stat3 was also detected in the majority (91%) of SGTs. The average combined scores for survivin and p-tyr Stat3 immunohistochemical expression in the studied malignant SGTs was 4.40 and 3.35, respectively; the corresponding combined scores for survivin and p-tyr Stat3 in the studied benign SGTs were 4.37 and 3.22, respectively. No statistically significant differences (P > .05) in p-tyr Stat3 or survivin expression were detected between the benign and malignant groups, or among the various examined histopathologic subtypes of SGTs. In contrast, normal salivary gland tissues revealed only weak and focal survivin or p-tyr Stat3 immunoreactivity, mainly localized to ductal and mucous cells.
Our data indicate an almost universal expression of activated Stat3 and survivin in benign and malignant SGTs. Considering the well established proliferative and antiapoptotic properties of these molecules and their functional interrelationship, selective targeting techniques against Stat3 and/or survivin may represent promising therapeutic strategies against neoplasms of salivary gland origin.
信号转导子和转录激活子3(Stat3)及生存素已被证明在多种人类肿瘤中发挥致癌作用。本研究的目的是评估酪氨酸磷酸化(活性)Stat3和生存素在各种良性和恶性涎腺肿瘤(SGTs)中的表达。
86例SGTs(65例恶性肿瘤和21例各种组织病理学亚型的良性肿瘤)用抗生存素或抗磷酸化酪氨酸-705(p-tyr)Stat3抗体进行免疫组织化学染色。免疫组织化学反应以半定量方式分级;通过将肿瘤细胞百分比(0-3)和染色强度(0-3)的个体评分相加,计算每个肿瘤的免疫组织化学阳性综合评分(0-6)。
在所有研究的良性和恶性SGTs中均检测到生存素免疫组织化学表达;在大多数(91%)SGTs中也检测到p-tyr Stat3。在研究的恶性SGTs中,生存素和p-tyr Stat3免疫组织化学表达的平均综合评分分别为4.40和3.35;在研究的良性SGTs中,生存素和p-tyr Stat3的相应综合评分分别为4.37和3.22。在良性和恶性组之间,或在SGTs的各种检查组织病理学亚型之间,未检测到p-tyr Stat3或生存素表达的统计学显著差异(P>.05)。相比之下,正常涎腺组织仅显示微弱和局灶性的生存素或p-tyr Stat3免疫反应性,主要定位于导管和黏液细胞。
我们的数据表明活化的Stat3和生存素在良性和恶性SGTs中几乎普遍表达。考虑到这些分子已确立的增殖和抗凋亡特性及其功能相互关系,针对Stat3和/或生存素的选择性靶向技术可能代表针对涎腺起源肿瘤的有前景的治疗策略。