title: Automated quantitative analysis of HDM2 expression in malignant melanoma shows association with early-stage disease and improved outcome.
abstract: The incidence of cutaneous malignant melanoma continues to increase every year, and this disease remains the leading cause of skin cancer death in industrialized countries. Despite the aggressive nature of advanced melanoma, there are no standard biological assays in clinical usage that can predict metastasis. This may be due, in part, to the inadequacy of reproducible assessment of protein expression using traditional immunohistochemistry. We have previously described a novel method of quantitative assessment of protein expression (AQUA) with the continuity and accuracy of an ELISA assay but with maintenance of critical spatial information. Here, we modify this technology for the evaluation of protein expression in melanoma. Using a tissue microarray cohort of 405 melanoma lesions and 17 normal skin samples, we analyzed expression of HDM2, the human homologue of murine double minute 2 with automated quantitative analysis. We show that expression levels in the nucleus are significantly higher in primary melanomas than in metastatic lesions. Furthermore, high levels of expression are predictive of better outcome. This study demonstrates that quantitative assessment of protein expression is useful in melanoma to validate potential tissue biomarkers and suggests that human homologue of murine double minute 2 may be a valuable prognostic tool for management of malignant melanoma.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Berger
authors.forename: Robert L
authors.initials: RL
authors.lastname: Camp
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Divito
authors.forename: Harriet M
authors.initials: HM
authors.lastname: Kluger
authors.forename: Ruth
authors.initials: R
authors.lastname: Halaban
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000096:biosynthesis*; D040081:Protein Array Analysis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051736:Proto-Oncogene Proteins c-mdm2; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2