This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mikhail, M. Articles by Osman, I. Search for Related Content PubMed PubMed Citation Articles by Mikhail, M. Articles by Osman, I.

PTEN Expression in Melanoma: Relationship with Patient Survival, Bcl-2 Expression, and Proliferation

Authors' Affilliations: Departments of ¹ Dermatology, ² Pathology, ³ Surgery, and ⁴ Medicine, New York University School of Medicine, and ⁵ Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York

Requests for reprints: Iman Osman, New York University School of Medicine, 550 First Avenue, H-100, New York, NY 10016. Phone: 212-686-7500 ext. 3522; Fax: 212-951-3214; E-mail: iman.osman{at}med.nyu.edu.

Purpose: Inactivation of the tumor suppressor gene, phosphatase and tensin homologue (PTEN), is a major alteration in preclinical melanoma models. We investigated the clinical relevance of PTEN expression in the primary melanoma patients with extended follow-up.

Experimental Design: We correlated PTEN expression with clinicopathologic variables and outcome in 127 primary melanomas (median follow-up, 12.8 years). We evaluated the associations between PTEN expression and proliferation and resistance to apoptosis (assessed by Ki-67 and Bcl-2, respectively). We also examined the effect of a favorable phenotype, defined as retained PTEN, low proliferative index, and low expression of Bcl-2 on disease-free survival and overall survival.

Results: Altered PTEN, Bcl-2, and Ki-67 expressions were observed in 55 of 127 (43.3%), 61 of 127 (48%), and 43 of 114 (37.7%) of cases, respectively. Decreased PTEN expression correlated significantly with the ulceration (P = 0.01). Rates of disease-free survival and overall survival in patients with favorable phenotype were 72% and 74% at 5 years versus 64% and 64% in patients with an unfavorable phenotype. At 10 years, the rates of disease-free survival and overall survival were 72% and 68% for patients with a favorable phenotype but declined to 60% and 55% in patients with an unfavorable phenotype. However, relationships between both PTEN and Bcl2 and patient survival were not significant as well as the associations between PTEN and Bcl-2 or Ki-67.

Conclusions: Our data suggest that altered PTEN expression is common in primary melanomas and is associated with aggressive tumor behavior. However, PTEN alone provided limited prognostic value. Our findings show the need to examine molecular alterations identified in preclinical studies using an adequately large cohort of patients with extended follow-up to better assess the magnitude of their clinical relevance.

This article has been cited by other articles:

				L. Packer, S. Pavey, A. Parker, M. Stark, P. Johansson, B. Clarke, P. Pollock, M. Ringner, and N. Hayward Osteopontin is a downstream effector of the PI3-kinase pathway in melanomas that is inversely correlated with functional PTEN Carcinogenesis, September 1, 2006; 27(9): 1778 - 1786. [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]

				A. Mirmohammadsadegh, A. Marini, S. Nambiar, M. Hassan, A. Tannapfel, T. Ruzicka, and U. R. Hengge Epigenetic Silencing of the PTEN Gene in Melanoma. Cancer Res., July 1, 2006; 66(13): 6546 - 6552. [Abstract] [Full Text] [PDF]