Decreasing expression of glucose-regulated protein GRP78/BiP as a significant prognostic predictor in patients with advanced laryngeal squamous cell carcinoma

作者：Kaira Kyoichi^*; Toyoda Minoru; Shimizu Akira; Imai Hisao; Sakakura Koichi; Nikkuni Osamu; Suzuki Masami; Iijima Misa; Asao Takayuki; Chikamatsu Kazuaki

来源：Head and Neck-Journal for the Sciences and Specialties of the Head and Neck, 2016, 38(10): 1539-1544.

DOI：10.1002/hed.24471

• endoplasmic reticulum stress
• glucose-regulated protein 78 (GRP78)
• immunoglobulin heavy chain binding protein (BiP)
• laryngeal cancer
• squamous cell carcinoma
• immunohistochemistry

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.

• 出版日期2016-10