Endothelin-1 in the tumor microenvironment correlates with melanoma invasion.

Endothelin-1 (ET-1) is a vasoactive peptide that also plays a role in the tanning response of the skin. Animal and cell culture studies have also implicated ET-1 in melanoma progression, but no association studies have been performed to link ET-1 expression and melanoma in humans. Here, we present the first in-vivo study of ET-1 expression in pigmented lesions in humans: an ET-1 immunohistochemical screen of melanocytic nevi, melanoma in situ lesions, invasive melanomas, metastatic melanomas, and blue nevi was performed. Twenty-six percent of melanocytic nevi and 44% of melanoma in situ lesions demonstrate ET-1 expression in the perilesional microenvironment, whereas expression in nevus or melanoma cells was rare to absent. In striking contrast, 100% of moderately to highly pigmented invasive melanomas contained numerous ET-1-positive cells in the tumor microenvironment, with 79% containing ET-1-positive melanoma cells, confirmed by co-staining with melanoma tumor marker HMB45. Hypopigmented invasive melanomas had reduced ET-1 expression, suggesting a correlation between ET-1 expression and pigmented melanomas. ET-1-positive perilesional cells were CD68-positive, indicating macrophage origin. Sixty-two percent of highly pigmented metastatic melanomas demonstrated ET-1 expression in melanoma cells, in contrast to 28.2% of hypopigmented specimens. Eighty-nine percent of benign nevi, known as blue nevi, which have a dermal localization, were associated with numerous ET-1-positive macrophages in the perilesional microenvironment, but no ET-1 expression was detected in the melanocytes. We conclude that ET-1 expression in the microenvironment increases with advancing stages of melanocyte transformation, implicating a critical role for ET-1 in melanoma progression, and the importance of the tumor microenvironment in the melanoma phenotype.

Mid- and long-term results of the treatment of infrainguinal arterial occlusive disease with precuffed expanded polytetrafluoroethylene grafts compared with vein grafts.

BACKGROUND: Prosthetic grafts for lower-extremity bypass have limited patency compared with autologous vein grafts. Precuffed expanded polytetrafluoroethylene (ePTFE) grafts alter the geometry of the distal hood to improve patency. This study reports the authors' long-term results on the use of precuffed ePTFE grafts for infrainguinal bypasses in patients with arterial occlusive disease and compares these with results of reversed great saphenous vein grafts (rSVG). METHODS: A retrospective review of billing codes identified 101 polytetrafluoroethylene (PTFE) and 47 rSVG bypasses performed over a 6-year period. Femoral to below-knee popliteal and femoral to tibial bypasses were analyzed. Data collected consisted of risk factors, Rutherford classification, bypass inflow and outflow, runoff vessels, patency, amputation, and death. Primary end points consisted of primary, assisted-primary, and secondary patency along with limb salvage. RESULTS: Mean age of the patients was 76 years in the PTFE group and 69.8 years in the rSVG group. For femoral to below-knee popliteal bypasses, primary patency at 1, 3, and 5 years in the PTFE group was 76.9%, 48.7%, and 43.3%, respectively, compared with 77.1%, 77.1%, and 77.1%, respectively, in the rSVG group (P = 0.225). Secondary patency was 89.2%, 70.9%, and 50.6% in the PTFE group compared with 84.4%, 84.4%, and 84.4% in the rSVG group (P = 0.269). Limb salvage was similar in the PTFE compared with the rSVG group (97.7%, 90.5%, and 79.4% vs. 83.3%, 83.3%, and 83.3%; P = 0.653). For femoral to tibial bypasses, primary patency in the PTFE group at 1, 3, and 5 years was 57.1%, 40.4%, and 22.1%, respectively, compared with 67.4%, 67.4%, and 50.6%, respectively, for the rSVG group (P = 0.246). Secondary patency was 75.5%, 44.9%, and 22.7% in the PTFE group compared with 91.8%, 91.8%, and 52.5% in the rSVG group (P = 0.022). Limb salvage at 1, 3, and 5 years was 79.2%, 55.7%, and 55.7%, respectively, in the PTFE group compared with 96.4%, 96.4%, and 64.3%, respectively, in the rSVG group (P = 0.046). CONCLUSIONS: Precuffed ePTFE grafts demonstrate similar 1-year patency to that of rSVG. However, mid- and long-term patency is reduced compared with saphenous vein grafts (SVG), especially to tibial targets. PTFE grafts to the popliteal demonstrate limb salvage rates similar to those of SVG. In the tibial vessels, limb salvage rates for PTFE grafts are significantly worse compared with SVG.