Immunologic escape and angiogenesis in human malignant melanoma.
BACKGROUND
Melanoma escape mechanisms include immunosuppressive and angiogenic cytokine production.


OBJECTIVE
We sought to determine vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression by immunohistochemistry, and soluble circulating plasma levels of VEGF, bFGF, IL-10, and transforming growth factor-beta2 in patients with different stages of melanoma.


METHODS
Biopsy specimens from 42 patients with primary melanoma and 9 with cutaneous metastases were studied by immunohistochemistry. In another 46 patients with melanoma (8 stage I and II; 18, III; and 20, IV) and in 10 healthy control participants, bFGF, VEGF, IL-10, and transforming growth factor-beta2 circulating levels were analyzed.


RESULTS
bFGF was positive in 85% and VEGF in 47.5% of 42 primary melanomas. Of 10 patients with primary melanoma (Breslow depth 1.5-3 mm) 6 were VEGF positive and had metastases develop, whereas 4 were VEGF negative and had no metastases at 5 years of follow up. VEGF, bFGF, and IL-10 plasma levels in patients with stages III and IV melanoma were higher than the control group (P <.05 and P <.01, respectively). An inverse relationship was found between VEGF and IL-10. Specifically, in 7 patients with IL-10 levels higher than 10 pg/mL, VEGF levels were less than 49 pg/mL (P <.05); in 9 patients with VEGF levels higher than 100 pg/mL, IL-10 levels were less than 6.7 pg/mL (P <.01).


CONCLUSIONS
VEGF expression in 1.5- to 3.0-mm Breslow depth melanomas may be considered as an unfavorable prognostic factor. Immunosuppressive (IL-10, transforming growth factor-beta2) and proangiogenic (bFGF, VEGF) cytokines are increased in metastatic melanoma. Inverse plasma levels between IL-10 and VEGF in patients with metastatic melanoma are shown in vivo for the first time, the significance of which must be further investigated.
Redondo
Pedro
P
Department of Dermatology, University Clinic of Navarra, School of Medicine, Pamplona, Spain. predondo@unav.es
Sánchez-Carpintero
Ignacio
I
Bauzá
Ana
A
Idoate
Michel
M
Solano
Teresa
T
Mihm
Martin C
MC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000378:metabolism* / Q000556:secondary; D008875:Middle Aged; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053781:Transforming Growth Factor beta2; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D043925:Angiogenesis Inducing Agents; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D016753:Interleukin-10