Patterns of GRP78 and MTJ1 expression in primary cutaneous malignant melanoma.
Cell surface expression of glucose-regulated protein 78 (GRP78) occurs in several types of cancer; however, its role in the behavior of primary cutaneous melanoma is not well studied. The association of cell surface GRP78 with other proteins such as MTJ1 stimulates cell proliferation. In this study, we characterized the pattern of expression of GRP78 and MTJ1 in invasive primary cutaneous melanomas and analyzed the relationships between the pattern of expression and various clinicopathological parameters. We found two patterns of GRP78 expression in invasive primary cutaneous melanoma. One pattern showed a gradual fading of protein expression from superficial to deeper levels within the same tumor. The second pattern of expression showed a similar fading with an abrupt regaining of expression at the deep invasive edge of the melanoma. These two distinct patterns of GRP78 expression correlated with both patient survival and depth of tumor invasion. A moderate MTJ1 expression was found to be associated with decreased patient survival; however, no significant associations were observed between patterns of GRP78 and MTJ1 expression. Our study (1) describes two distinct patterns of GRP78 in invasive primary cutaneous melanoma, (2) inversely correlates regain of GRP78 expression with patient survival, and (3) suggests a modifying effect of MTJ1 on GRP78 in enhancing tumor aggressiveness.
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. papal002@mc.duke.edu
John A
JA
Papalas
Robin T
RT
Vollmer
Mario
M
Gonzalez-Gronow
Salvatore V
SV
Pizzo
James
J
Burchette
Kenneth E
KE
Youens
Krystal B
KB
Johnson
Maria A
MA
Selim
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D050956:HSP40 Heat-Shock Proteins / Q000096:biosynthesis*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
D014408:Biomarkers, Tumor; C485368:DNAJC1 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D050956:HSP40 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008565:Membrane Proteins