This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dai, D. L. Articles by Li, G. Search for Related Content PubMed PubMed Citation Articles by Dai, D. L. Articles by Li, G.

Prognostic Significance of Activated Akt Expression in Melanoma: A Clinicopathologic Study of 292 Cases

From the Department of Medicine, Division of Dermatology; Department of Pathology, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.

Address reprint requests to Gang Li, MD, Jack Bell Research Centre, 2660 Oak St, Vancouver, BC V6H 3Z6, Canada; e-mail: gangli{at}interchange.ubc.ca

PURPOSE: Akt is a serine/threonine kinase that leads to stimulation of cell cycle progression, cell proliferation, and inhibition of apoptosis. To investigate the role of Akt in melanoma pathogenesis, we examined the expression of phospho-Akt (p-Akt; Ser-473) in melanocytic lesions at different stages and analyzed the correlations between the p-Akt expression level and clinicopathologic factors and patient survival.

PATIENTS AND METHODS: We evaluated the p-Akt expression in 12 cases of normal nevi, 58 cases of dysplastic nevi, 170 cases of primary melanomas, and 52 cases of melanoma metastases using tissue microarray and immunohistochemistry.

RESULTS: Strong p-Akt expression was observed in 17%, 43%, 49%, and 77% of the biopsies in normal nevi, dysplastic nevi, primary melanoma, and melanoma metastases, respectively. Significant differences for p-Akt staining pattern were observed between normal nevi and primary melanomas (P < .05), and between primary melanomas and melanoma metastases (P < .001). Furthermore, our Kaplan-Meier survival curves showed that strong p-Akt expression is inversely correlated with both overall and disease-specific 5-year survival of patients with primary melanoma (P < .05 for both). Strikingly, our multivariate Cox regression analysis revealed that p-Akt is an independent prognostic factor in low-risk melanomas (thickness 1.5 mm; relative risk, 6.44; 95% CI, 1.28 to 32.55; P = .018).

CONCLUSION: The expression of p-Akt increases dramatically with melanoma invasion and progression and is inversely correlated with patient survival. In addition, p-Akt may serve as an independent prognostic marker and help to identify those patients with low-risk melanomas who are at increased risk of death.

Supported by the National Cancer Institute of Canada.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

This article has been cited by other articles:

				T. Sittler, J. Zhou, J. Park, N. K. Yuen, S. Sarantopoulos, J. Mollick, R. Salgia, A. Giobbie-Hurder, G. Dranoff, and F. S. Hodi Concerted Potent Humoral Immune Responses to Autoantigens Are Associated with Tumor Destruction and Favorable Clinical Outcomes without Autoimmunity Clin. Cancer Res., June 15, 2008; 14(12): 3896 - 3905. [Abstract] [Full Text] [PDF]

				M. Cheung, A. Sharma, S. V. Madhunapantula, and G. P. Robertson Akt3 and Mutant V600EB-Raf Cooperate to Promote Early Melanoma Development Cancer Res., May 1, 2008; 68(9): 3429 - 3439. [Abstract] [Full Text] [PDF]

				P. Jiang, A. Enomoto, M. Jijiwa, T. Kato, T. Hasegawa, M. Ishida, T. Sato, N. Asai, Y. Murakumo, and M. Takahashi An Actin-Binding Protein Girdin Regulates the Motility of Breast Cancer Cells Cancer Res., March 1, 2008; 68(5): 1310 - 1318. [Abstract] [Full Text] [PDF]

				J. A. Crowell, V. E. Steele, and J. R. Fay Targeting the AKT protein kinase for cancer chemoprevention Mol. Cancer Ther., August 1, 2007; 6(8): 2139 - 2148. [Abstract] [Full Text] [PDF]

				Y. Wang, D. L. Dai, M. Martinka, and G. Li Prognostic Significance of Nuclear ING3 Expression in Human Cutaneous Melanoma Clin. Cancer Res., July 15, 2007; 13(14): 4111 - 4116. [Abstract] [Full Text] [PDF]

				A. M. Karst, D. L. Dai, J. Q. Cheng, and G. Li Role of p53 Up-regulated Modulator of Apoptosis and Phosphorylated Akt in Melanoma Cell Growth, Apoptosis, and Patient Survival. Cancer Res., September 15, 2006; 66(18): 9221 - 9226. [Abstract] [Full Text] [PDF]

				K. Gao, D. L. Dai, M. Martinka, and G. Li Prognostic Significance of Nuclear Factor-{kappa}B p105/p50 in Human Melanoma and Its Role in Cell Migration. Cancer Res., September 1, 2006; 66(17): 8382 - 8388. [Abstract] [Full Text] [PDF]

				L. S. Spofford, E. V. Abel, K. Boisvert-Adamo, and A. E. Aplin Cyclin D3 Expression in Melanoma Cells Is Regulated by Adhesion-dependent Phosphatidylinositol 3-Kinase Signaling and Contributes to G1-S Progression J. Biol. Chem., September 1, 2006; 281(35): 25644 - 25651. [Abstract] [Full Text] [PDF]

				L. Chin, L. A. Garraway, and D. E. Fisher Malignant melanoma: genetics and therapeutics in the genomic era. Genes & Dev., August 15, 2006; 20(16): 2149 - 2182. [Abstract] [Full Text] [PDF]

				R Bauer, P J Wild, S Meyer, F Bataille, A Pauer, M Klinkhammer-Schalke, F Hofstaedter, and A K Bosserhoff Prognostic relevance of P-cadherin expression in melanocytic skin tumours analysed by high-throughput tissue microarrays J. Clin. Pathol., July 1, 2006; 59(7): 699 - 705. [Abstract] [Full Text] [PDF]

				C. A. Granville, R. M. Memmott, J. J. Gills, and P. A. Dennis Handicapping the Race to Develop Inhibitors of the Phosphoinositide 3-Kinase/Akt/Mammalian Target of Rapamycin Pathway Clin. Cancer Res., February 1, 2006; 12(3): 679 - 689. [Abstract] [Full Text] [PDF]

				J. Tsurutani, J. Fukuoka, H. Tsurutani, J. H. Shih, S. M. Hewitt, W. D. Travis, J. Jen, and P. A. Dennis Evaluation of Two Phosphorylation Sites Improves the Prognostic Significance of Akt Activation in Non-Small-Cell Lung Cancer Tumors J. Clin. Oncol., January 10, 2006; 24(2): 306 - 314. [Abstract] [Full Text] [PDF]