Expression of 12-lipoxygenase as a biomarker for melanoma carcinogenesis.
12-Lipoxygenase (12-LOX), through its metabolite 12( )-hydroxyeicosatetraenoic acid [12( )-HETE], has been demonstrated to play a pivotal role in experimental melanoma invasion and metastasis, and 12-LOX expression may be important in early human melanoma carcinogenesis. We have studied the differences in 12-LOX protein expression during the progression of melanoma from human melanocytic cells to benign and dysplastic naevi to malignant metastatic disease. 12-LOX expression was determined in normal human skin melanocytes and in melanocytes found in compound naevi, dysplastic naevi and melanomas using a platelet-type 12-LOX antibody with a diaminobenzidine immunoperoxidase system detection system and was quantified using the analysis software NIH Image 1.62. Mean cellular pixel densities for 12-LOX staining ( = 50 cells/histological type) were unchanged in compound naevi ( = 0.14) and were increased in dysplastic naevi and melanomas compared with normal skin melanocytes ( = 0.03 and = 0.01, respectively). Similarly, melanomas had higher levels of expression compared with dysplastic naevi ( = 0.03). 12-LOX expression was significantly different between compound naevus and dysplastic naevus melanocytes ( = 0.01). These data suggest that 12-LOX may be an important novel marker for cancer progression within the melanoma system, and therefore could be a useful biomarker and therapeutic target for melanoma chemoprevention.
Winer
I
I
Department of Internal Medicine, University of Michigan Medical School and VA Medical Center, Ann Arbor, Michigan 48109, USA.
Normolle
D P
DP
Shureiqi
I
I
Sondak
V K
VK
Johnson
T
T
Su
L
L
Brenner
D E
DE
D001092:Arachidonate 12-Lipoxygenase / Q000096:biosynthesis*; D001792:Blood Platelets / Q000201:enzymology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008544:Melanocytes / Q000201:enzymology; D008545:Melanoma / Q000175:diagnosis* / Q000201:enzymology*; D009506:Nevus / Q000201:enzymology; D011230:Precancerous Conditions; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000201:enzymology*
D001092:Arachidonate 12-Lipoxygenase