PTEN expression in melanoma: relationship with patient survival, Bcl-2 expression, and proliferation.
OBJECTIVE
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.


METHODS
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.
Mikhail
Maryann
M
Department of Dermatology, New York University School of Medicine, New York, New York 10016, USA.
Velazquez
Elsa
E
Shapiro
Richard
R
Berman
Russell
R
Pavlick
Anna
A
Sorhaindo
Lian
L
Spira
Joanna
J
Mir
Carmen
C
Panageas
Katherine S
KS
Polsky
David
D
Osman
Iman
I
D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D051059:PTEN Phosphohydrolase; D010641:Phenotype; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human