Molecular oncogene markers and their significance in cutaneous malignant melanoma.
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.
Konstadoulakis
M M
MM
Department of Surgery, Brown University School of Medicine, Center for Statistical Science, Providence, Rhode Island, USA.
Vezeridis
M
M
Hatziyianni
E
E
Karakousis
C P
CP
Cole
B
B
Bland
K I
KI
Wanebo
H J
HJ
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
D014408:Biomarkers, Tumor; D006684:HLA-DR Antigens; D018840:HSP70 Heat-Shock Proteins; D016271:Proto-Oncogene Proteins c-myc