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 (T(1) and T(2)). 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.
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 (T(1) and T(2)). 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.
Authors: Keziban Unsal-Kacmaz; Shoba Ragunathan; Edward Rosfjord; Stephen Dann; Erik Upeslacis; Mary Grillo; Richard Hernandez; Fiona Mack; Anke Klippel Journal: Mol Oncol Date: 2011-12-28 Impact factor: 6.603
Authors: Bisrat G Debeb; Xiaomei Zhang; Savitri Krishnamurthy; Hui Gao; Evan Cohen; Li Li; Angel A Rodriguez; Melissa D Landis; Anthony Lucci; Naoto T Ueno; Fredika Robertson; Wei Xu; Lara Lacerda; Thomas A Buchholz; Massimo Cristofanilli; James M Reuben; Michael T Lewis; Wendy A Woodward Journal: Mol Cancer Date: 2010-07-08 Impact factor: 27.401
Authors: Joseph A Sparano; Stacy Moulder; Aslamuzzaman Kazi; Domenico Coppola; Abdissa Negassa; Linda Vahdat; Tianhong Li; Christine Pellegrino; Susan Fineberg; Pam Munster; Mokenge Malafa; David Lee; Shira Hoschander; Una Hopkins; Dawn Hershman; John J Wright; Celina Kleer; Sofia Merajver; Said M Sebti Journal: Clin Cancer Res Date: 2009-04-07 Impact factor: 12.531