Expression of 12-lipoxygenase as a biomarker for melanoma... : Melanoma Research (original) (raw)

Original Articles

Winer, I.; Normolle, D. P.; Shureiqi, I.; Sondak, V. K.; Johnson, T.; Su, L.; Brenner, D. E.*

Departments of Internal Medicine and Pharmacology (I. Winer, D. E. Brenner), Radiation Oncology (D. P. Normolle), Surgery (V. K. Sondak, T. Johnson), Dermatology (T. Johnson), Otolaryngology (T. Johnson) and Pathology (L. Su), University of Michigan Medical School and VA Medical Center, Ann Arbor, Michigan, USA. Department of Clinical Cancer Prevention, MD Anderson Cancer Center, Houston, Texas, USA (I. Shureiqi).

*To whom correspondence should be addressed at 2150 Cancer and Geriatrics Center, University of Michigan Medical Center, Ann Arbor, MI 48109-0930, USA. Tel: (+1) 734 647 1417; Fax: (+1) 734 647 9817; Email: [email protected]

(Received 13 July 2001; accepted in revised form 29 December 2001)

Abstract

12-Lipoxygenase (12-LOX), through its metabolite 12(S)-hydroxyeicosatetraenoic acid [12(S)-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 (n = 50 cells/histological type) were unchanged in compound naevi (P = 0.14) and were increased in dysplastic naevi and melanomas compared with normal skin melanocytes (P = 0.03 and P = 0.01, respectively). Similarly, melanomas had higher levels of expression compared with dysplastic naevi (P = 0.03). 12-LOX expression was significantly different between compound naevus and dysplastic naevus melanocytes (P = 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.