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



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.



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).



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. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1544, 2016.
Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Gunma, Japan. kkaira1970@yahoo.co.jp.
Kyoichi
K
Kaira
Department of Otolaryngology - Head and Neck Surgery, Gunma University Graduate School of Medicine, Gunma, Japan.
Minoru
M
Toyoda
Department of Dermatology, Gunma University Graduate School of Medicine, Gunma, Japan.
Akira
A
Shimizu
Department of Respiratory Medicine, Gunma Prefectural Cancer Center, Gunma, Japan.
Hisao
H
Imai
Department of Otolaryngology - Head and Neck Surgery, Gunma University Graduate School of Medicine, Gunma, Japan.
Koichi
K
Sakakura
Department of Otolaryngology - Head and Neck Surgery, Gunma University Graduate School of Medicine, Gunma, Japan.
Osamu
O
Nikkuni
Department of Head and Neck Surgery, Gunma Prefectural Cancer Center, Gunma, Japan.
Masami
M
Suzuki
Department of Pathology and Clinical Laboratories, Gunma Prefectural Cancer Center, Gunma, Japan.
Misa
M
Iijima
Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Gunma, Japan.
Takayuki
T
Asao
Department of Otolaryngology - Head and Neck Surgery, Gunma University Graduate School of Medicine, Gunma, Japan.
Kazuaki
K
Chikamatsu
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D015996:Survival Rate
D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins
endoplasmic reticulum stress; glucose-regulated protein 78 (GRP78); immunoglobulin heavy chain binding protein (BiP); immunohistochemistry; laryngeal cancer; squamous cell carcinoma