The Prognostic Value of Ki-67, p53, 1p36, and 9p21 in Skull Base Chordomas
C Horbinski, GJ Oakley, K Cieply, RR Seethala. University of Pittsburgh, Pittsburgh, PA
Background: Skull base chordomas (CD) are rare, locally aggressive, notochord-derived neoplasms for which prognostic biomarkers are not well established. We evaluate the relevance of Ki-67 and p53 protein expression as well as 1p36 and 9p21 loss, all of which are markers of recent interest in the literature, to the biology and behavior of CD.
Design: 15 skull base CD (collected from 1980 2007) were evaluated by dual-color FISH analysis for the 1p36 and 9p21 chromosomal regions. For 1p36 hybridization was performed using a spectrum orange labeled probe for 1p36 and spectrum green labeled control probe for 1q25 (Vysis dual-color probe set, LSI 1p36/LSI 1p25) Vysis, Downers Grove, IL, USA). For 9p21 hybridization was performed using a spectrum orange labeled probe for CDKN2A (p16) and a spectrum green labeled chromosome 9 centromeric probe (CEP 9) (Vysis, Downers Grove, IL, USA). Cases were considered positive for 1p36 deletion if 20% of nuclei showed deletion. For 9p21 only homozygous deletion was counted and was defined by loss of both 9p21 signals in 20% of nuclei with least one CEP 9 signal. Additionally, immunohistochemical staining for p53 (1:100, DO7, Dako, Carpinteria, CA) and Ki-67 (1:25, ki-55, Dako) were performed. Results were then correlated with clinical and pathologic parameters.
Results: Loss at 1p36 or homozygous deletion at 9p21 were in 4/15 (26.7%) with 2 cases (13.3%) showing deletion of both loci. All cases with 1p36 deletion, and all but one case with 9p21 deletion, were conventional CD. 1p36 loss was equally distributed between CD with and without prominent solid components (2 cases each), while 9p21 deletion was more frequent (3/4 cases) in tumors with a prominent solid component. Neither the deletions nor p53 expression were significant predictors of overall survival (1p36: log rank p=0.599, 9p21: p=0.363, p53: p=0.647). However, a Ki-67 index of greater than 5% predicted a worse outcome (p=0.002).
Conclusions: Ki-67 is the only marker predictive of outcome in this small series. There is a tendency for loss of 1q36 and 9p21 to occur with more 'aggressive' histologies, namely conventional CD and CD with prominent solid components. However, this study does not support these loci as major prognosticators for this tumor.
Category: Head & Neck
Monday, March 9, 2009 1:00 PM
Poster Session II # 176, Monday Afternoon