title: Clinical and Pathological Significance of ER Stress Marker (BiP/GRP78 and PERK) Expression in Malignant Melanoma.
abstract: Glucose-regulated protein of 78 kD (GRP78) also referred to as immunoglobulin heavy chain binding protein (BiP/GRP78) plays an important role in the endoplasmic reticulum (ER) stress. The level of BiP/GRP78 is highly elevated in various human cancers. The purpose of this study is to examine the prognostic significance of BiP/GRP78 expression in patients with malignant melanoma. A total of 133 malignant melanoma patients were analyzed, and tumor specimens were stained by immunohistochemistry for BiP/GRP78, PKR-like endoplasmic reticulum kinase (PERK), Ki-67, p53 and microvessel density (MVD) determined by CD34. BiP/GRP78 and PERK were highly expressed in 40 % (53/133) and 78 % (104/133), respectively. BiP/GRP78 disclosed a significant relationship with PERK expression, thickness, T factor, N factor, disease staging, cell proliferation (Ki-67) and MVD (CD34). By multivariate analysis, the high expression of BiP/GRP78 was identified as an independent prognostic factor for predicting poor survival against malignant melanoma. The increased BiP/GRP78 expression was clarified as an independent prognostic marker for predicting worse outcome. ER stress marker, BiP/GRP78 could be a powerful molecular target for the treatment of malignant melanoma.
authors: Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan. shimizuakira@gunma-u.ac.jp.
authors: Akira
authors: A
authors: Shimizu
authors: Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors: Kyoichi
authors: K
authors: Kaira
authors: Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors: Masahito
authors: M
authors: Yasuda
authors: Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors: Takayuki
authors: T
authors: Asao
authors: Department of Dermatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors: Osamu
authors: O
authors: Ishikawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D011379:Prognosis; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D019394:Ki-67 Antigen; C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase
keywords: BiP/GRP78; ER stress; Immunohistochemistry; Malignant melanoma; PERK; Prognosis; Skin cancer