Expression of glucose-regulated stress protein GRP78 is related to progression of melanoma.
OBJECTIVE
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.


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 (chi(2) = 8.0703, P = 0.0045) and overall survival (chi(2) = 6.2633, P = 0.0123) in melanoma patients with IRS >25 were significantly lower than in melanoma patients with IRS <25.


CONCLUSIONS
GRP78 expression appears to correlate with known correlates of melanoma progression and survival and requires further evaluation as a prognostic biomarker in melanoma.
Zhuang
Liquing
L
Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
Scolyer
Richard A
RA
Lee
C Soon
CS
McCarthy
Stanley W
SW
Cooper
Wendy A
WA
Zhang
Xu D
XD
Thompson
John F
JF
Hersey
Peter
P
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018572:Disease-Free Survival; D004416:Dysplastic Nevus Syndrome / Q000378:metabolism / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D008875:Middle Aged; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism*; D009506:Nevus / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015996:Survival Rate
D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones