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Expression of glucose-regulated stress protein GRP78 is related to progression of melanoma |
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| Authors: | Liquing Zhuang Richard A Scolyer C Soon Lee Stanley W McCarthy Wendy A Cooper Xu D Zhang John F Thompson & Peter Hersey |
| Institution: | Department of Anatomical Pathology;, Sydney Melanoma Unit, Royal Prince Alfred Hospital, Sydney;, Discipline of Pathology, Faculty of Medicine, The University of Sydney, Sydney;, Oncology and Immunology Unit, Newcastle Mater Misericordiae Hospital, Newcastle;, and Discipline of Surgery, Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia |
| Abstract: | Aims: Glucose-regulated protein 78 (GRP78) is a protein translated in response to endoplasmic reticulum (ER) stress that has been implicated in the pathogenesis and resistance to therapy of a variety of cancers. The aim of this study was to investigate its expression and role in the development and progression of human melanoma. Methods and results: The immunohistochemical expression of GRP78 in naevi, primary melanoma and melanoma metastases from 171 patients was correlated with clinicopathological factors and patient survival. The GRP78 immunoreactivity score (IRS) was 0.2 in compound naevi, 0.65 in dysplastic naevi, 4.65 in naevi adjacent to primary melanoma, 2.4 in melanoma in situ , 11.2 in thin (≤1.0 mm) and 18.1 in thick (>1.0 mm) primary melanoma. It was 18 and 17.3 in subcutaneous and lymph node metastases, respectively ( P < 0.0001). GRP78 expression was positively correlated with increasing tumour thickness ( P = 0.001) and with increasing dermal tumour mitotic index ( P = 0.0004). Disease-free survival (χ Conclusions: GRP78 expression appears to correlate with known correlates of melanoma progression and survival and requires further evaluation as a prognostic biomarker in melanoma. |
| Keywords: | endoplasmic reticulum glucose-regulated protein 78 melanocytic lesions melanoma pathogenesis stress protein |