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. Modern Pathology ( 2010) 23, 134-143; doi: 10.1038/modpathol.2009.152; published online 16 October 2009