Kleer Celina G, Teknos Theodoros N, Islam Mozaffarul, Marcus Benjamin, Lee Julia Shin-Jung, Pan Quintin, Merajver Sofia D
Department of Pathology, University of Michigan, Ann Arbor, 48109, USA.
Clin Cancer Res. 2006 Aug 1;12(15):4485-90. doi: 10.1158/1078-0432.CCR-06-0376.
Survival rates for squamous cell carcinoma of the head and neck (SCCHN) have remained unchanged for several decades due to local tumor recurrences as well as regional and distant metastases. Recent evidence has shown that RhoC GTPase is overexpressed in stages III and IV regionally metastatic SCCHN compared with stages I and II localized disease. This study evaluated the expression of RhoC in head and neck carcinoma and investigated the prognostic use of this marker on a large cohort of previously untreated patients with SCCHN.
Standard Western blot techniques were used to evaluate RhoC protein expression in nine established head and neck cancer cell lines and in normal oral epithelium. In vivo expression of RhoC in metastatic and nonmetastatic SCCHN was investigated using immunohistochemical analysis on a tissue microarray composed of 113 independent tumor samples. RhoC expression was analyzed as it related to clinical and pathologic variables of interest.
Levels of RhoC protein were increased in the SCCHN cell lines compared with normal oral epithelium. The in vivo expression of RhoC correlated with advanced clinical stage and lymph node metastases for the entire patient cohort as well as in small primary tumors (T(1) and T(2)).
This study is the first to examine the expression of RhoC GTPase protein in SCCHN and normal squamous epithelium. It is clear from the results that RhoC is a specific marker of lymph node metastases in patients with this challenging form of carcinoma. RhoC levels seem to identify a subset of patients with early tumor stage primary tumors and high metastatic potential that might benefit from more aggressive therapy. Through continued investigation, blockade of RhoC activity may be a potential target in the development of novel strategies for treating metastases of head and neck cancer.
由于局部肿瘤复发以及区域和远处转移，头颈部鳞状细胞癌（SCCHN）的生存率几十年来一直没有变化。最近的证据表明，与I期和II期局限性疾病相比，RhoC GTP酶在III期和IV期区域转移性SCCHN中过度表达。本研究评估了RhoC在头颈部癌中的表达，并在一大群未经治疗的SCCHN患者中研究了该标志物的预后用途。
使用标准的蛋白质印迹技术评估RhoC蛋白在9种已建立的头颈部癌细胞系和正常口腔上皮中的表达。通过对由113个独立肿瘤样本组成的组织微阵列进行免疫组织化学分析，研究RhoC在转移性和非转移性SCCHN中的体内表达。分析RhoC表达与感兴趣的临床和病理变量的关系。
与正常口腔上皮相比，SCCHN细胞系中RhoC蛋白水平升高。RhoC的体内表达与整个患者队列以及小的原发性肿瘤（T(1)和T(2)）的晚期临床分期和淋巴结转移相关。
本研究首次检测了RhoC GTP酶蛋白在SCCHN和正常鳞状上皮中的表达。从结果可以清楚地看出，RhoC是这种具有挑战性的癌症患者淋巴结转移的特异性标志物。RhoC水平似乎可以识别出早期肿瘤阶段原发性肿瘤且具有高转移潜能的一部分患者，这些患者可能从更积极的治疗中获益。通过持续研究，阻断RhoC活性可能是开发治疗头颈部癌转移新策略的潜在靶点。
