title: Molecular oncogene markers and their significance in cutaneous malignant melanoma.
abstract: BACKGROUND
  Oncogenes and other molecular tumor markers that predict tumor aggressiveness may allow individualization and optimization of surgical therapy of intermediate-thickness malignant melanoma. We examined the expression of selected markers, including the HLA-DR antigen, the heat shock protein-70 (HSP-70), and the c-myc oncogene in primary melanoma and regional nodes and related these findings to metastatic potential and survival.
  
  
  METHODS
  Forty patients with primary melanoma (1.5-4.0 mm) were studied, all of whom had prophylactic lymph node dissection and were followed for 18 months to 7 years. The primary tissue and nodes were examined using immunohistochemical techniques for the presence of HLA-DR antigen and HSP-70 protein and the expression of the c-myc oncogene.
  
  
  RESULTS
  Of 40 patients, there were 23 with lesions 1 to 2.9 mm thick and 17 with lesions 3 to 4 mm thick. Nodal metastases were present in 25 of the 40 patients who had elective node dissection. HLA-DR antibody stained the primary tumor in 10 patients (25%), but there was no correlation with survival in this group. HLA-DR antibody stained the stroma and cellular infiltrates surrounding the primary tumor in 28 of 40 patients; in this group there was a correlation of HLA-DR staining of the peritumoral stroma with improved survival overall. HLA-DR staining of the peritumoral stroma also influenced survival when patients were stratified by tumor thickness groups 1 to 2.9 mm and 3 to 4 mm and presence of nodal metastases. HSP-70 was demonstrated in the primary tumor in 25% of patients, who were also shown to have significantly improved survival when compared with those whose primary tumor did not stain with HSP-70. C-myc was expressed in the primary tumor in 25%, but showed no correlation with survival. None of these proteins correlated with or predicted the presence of nodal metastases.
  
  
  CONCLUSIONS
  We conclude that the use of specific molecular-oncogene markers in intermediate-thickness primary melanoma may identify patients at high risk for conventional treatment failure and reduced survival who may profit from more aggressive surgery, adjuvant therapy, or both.
authors.affiliation: Department of Surgery, Brown University School of Medicine, Center for Statistical Science, Providence, Rhode Island, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Konstadoulakis
authors.forename: M
authors.initials: M
authors.lastname: Vezeridis
authors.forename: E
authors.initials: E
authors.lastname: Hatziyianni
authors.forename: C P
authors.initials: CP
authors.lastname: Karakousis
authors.forename: B
authors.initials: B
authors.lastname: Cole
authors.forename: K I
authors.initials: KI
authors.lastname: Bland
authors.forename: H J
authors.initials: HJ
authors.lastname: Wanebo
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006684:HLA-DR Antigens / Q000032:analysis*; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis*; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D016019:Survival Analysis; D017211:Treatment Failure
chemical_list: D014408:Biomarkers, Tumor; D006684:HLA-DR Antigens; D018840:HSP70 Heat-Shock Proteins; D016271:Proto-Oncogene Proteins c-myc