Kyoichi Kaira1, Minoru Toyoda2, Akira Shimizu3, Hisao Imai4, Koichi Sakakura2, Osamu Nikkuni2, Masami Suzuki5, Misa Iijima6, Takayuki Asao7, Kazuaki Chikamatsu2. 1. Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Gunma, Japan. kkaira1970@yahoo.co.jp. 2. Department of Otolaryngology - Head and Neck Surgery, Gunma University Graduate School of Medicine, Gunma, Japan. 3. Department of Dermatology, Gunma University Graduate School of Medicine, Gunma, Japan. 4. Department of Respiratory Medicine, Gunma Prefectural Cancer Center, Gunma, Japan. 5. Department of Head and Neck Surgery, Gunma Prefectural Cancer Center, Gunma, Japan. 6. Department of Pathology and Clinical Laboratories, Gunma Prefectural Cancer Center, Gunma, Japan. 7. Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Gunma, Japan.
Abstract
BACKGROUND: The immunoglobulin heavy chain binding protein (BiP)/glucose-regulated protein 78 (GRP78) is important in the endoplasmic reticulum stress, and is highly expressed in various human cancers. The clinical and pathological features of GRP78/BiP are unclear in patients with advanced laryngeal squamous cell carcinoma (SCC). The purpose of this study was to investigate the clinicopathological significance of GRP78/BiP as a prognostic marker for laryngeal SCC. METHODS: A total of 59 patients with advanced laryngeal SCC (stage III/IV) were analyzed, and tumor specimens were stained by immunohistochemistry for GRP78/BiP and Ki-67. Microvessel density was determined by immunohistochemical staining for CD34 and p53. RESULTS: Expression of GRP78/BiP was confirmed in 87% of cases. Decreased expression of GRP78/BiP was highly associated with positive expression of p53. Decreased GRP78/BiP expression was identified on multivariate analysis as an independent factor of decreased progression-free survival (PFS). CONCLUSION: GRP78/BiP was found to be commonly expressed in laryngeal SCC, whereas its downregulation was found to serve a significant prognostic role for predicting poor survival in patients with laryngeal SCC with advanced disease. GRP78/BiP may be a potentially attractive target for the treatment of various human neoplasms.
BACKGROUND: The immunoglobulin heavy chain binding protein (BiP)/glucose-regulated protein 78 (GRP78) is important in the endoplasmic reticulum stress, and is highly expressed in various humancancers. The clinical and pathological features of GRP78/BiP are unclear in patients with advanced laryngeal squamous cell carcinoma (SCC). The purpose of this study was to investigate the clinicopathological significance of GRP78/BiP as a prognostic marker for laryngeal SCC. METHODS: A total of 59 patients with advanced laryngeal SCC (stage III/IV) were analyzed, and tumor specimens were stained by immunohistochemistry for GRP78/BiP and Ki-67. Microvessel density was determined by immunohistochemical staining for CD34 and p53. RESULTS: Expression of GRP78/BiP was confirmed in 87% of cases. Decreased expression of GRP78/BiP was highly associated with positive expression of p53. Decreased GRP78/BiP expression was identified on multivariate analysis as an independent factor of decreased progression-free survival (PFS). CONCLUSION:GRP78/BiP was found to be commonly expressed in laryngeal SCC, whereas its downregulation was found to serve a significant prognostic role for predicting poor survival in patients with laryngeal SCC with advanced disease. GRP78/BiP may be a potentially attractive target for the treatment of various humanneoplasms.