PTEN (10q) Loss Occurs in a Subset of Pilocytic Astrocytomas with Anaplastic Transformation
EF Rodriguez, BW Scheithauer, C Giannini, A Rynearson, FJ Rodriguez. Mayo Clinic College of Medicine, Rochester, MN
Background: Pilocytic astrocytoma (PA) is a low grade astrocytic tumor that occurs most commonly in children and young adults. Anaplastic (malignant) transformation of PA is an extremely rare event. No studies of the molecular characteristics of this phenomenon exist in the literature to our knowledge.
Design: We studied 12 PA obtained from 9 males and 3 females with a median age of 28.5 years at the time of malignant transformation (range 11-73). The tumors occurred at a variety of sites, including cerebellum (n=5), supratentorial brain (n=3), spinal cord (n=2), brainstem (n=1) and tectum (n=1). Relevant clinical features included NF1 (n=4) and prior irradiation (n=1). Histologic slides were evaluated by three (of 4) observers (EFR, CG, FJR, BWS). Anaplastic transformation was defined by the presence of brisk mitotic activity (>5/10 HPF) with or without endothelial proliferation or necrosis. We performed dual color fluorescence in situ hybridization (FISH) studies, using LSI probes targeting PTEN (10q23)(n=12) and EGFR (7p12) (n=10) with respective CEP10 and CEP7 control probes. A total of100 cells/per case were counted by 2 independent observers. A third independent observer scored discordant cases. Immunohistochemical (IHC) studies for ki-67(MIB-1)(n=11) and P53 (n=10) were also performed.
Results: Clinical follow-up was available in 9 patients: 5 developed tumor recurrences and 4 expired 5 mos to 2 yrs after surgery. Histologic evaluation showed a median mitotic count/10 HPF of 8, necrosis (n=7) and endothelial proliferation (n=2). Results of FISH and IHC studies are summarized in table 1. There were no associations between molecular abnormalities and clinical features or survival. However, the only two PA arising in the spinal cord had PTEN (10q) deletion.
Conclusions: PTEN (10q) deletion is present in 25% of cases in our series of PA with anaplastic transformation. Although gains of chromosome 7 were frequent, EGFR amplification was not identified in any case. Further molecular studies using additional markers are necessary to better characterize the oncogenic mechanisms responsible for anaplastic transformation in PA.
FISH and IHC studies in the malignant component of pilocytic astrocytomas with anaplastic transformation
|PTEN (10q) heterozygous deletion||3/12 (25)|
|Chr 7 gain||8/10 (80)|
|EGFR amplification||0/10 (0)|
|P53 overexpression (3+)||3/10 (30)|
|MIB1 labeling index||Median 22% (range 4-63)|
Monday, March 9, 2009 2:00 PM
Platform Session: Section H, Monday Afternoon