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RhoC GTPase Expression as a Potential Marker of Lymph Node Metastasis in Squamous Cell Carcinomas of the Head and Neck

Authors' Affiliations: Departments of ¹ Pathology, ² Biostatistics, ³ Internal Medicine, and ⁴ Otolaryngology-Head and Neck Surgery and ⁵ Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan

Requests for reprints: Theodoros N. Teknos, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, 1904 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109. Phone: 734-936-3172; Fax: 734-936-9625; E-mail: teknos{at}umich.edu.

Purpose: 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.

Experimental Design: 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.

Results: 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 (T₁ and T₂).

Conclusions: 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.

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