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Molecular
markers predictive of disease outcome in medulloblastoma
A.
J. Gajjar, R. Hernan, C. Fuller, Y. Lee, M. Kocak, C. Lau, M. Chintagumpala, D.
Ashley, S. Kellie, R. Gilbertson
St
Jude Children's Rsrch Hosp, Memphis, TN; Texas Children's Hospital, Houston, TX;
Royal Children's Hospital, Melbourne, Australia; Children's Hospital at
Westmead, Sydney, Australia
At
present there are no established molecular prognostic factors for
medulloblastoma (MB).
Therefore, we employed western blotting and real-time PCR analysis of fresh
frozen tumors to determine the prognostic significance of ERBB2, TRKC, MYCC and
MYCN expression among 86 children diagnosed with MB between 1984-2002.
Patients were fully staged and all received craniospinal radiation therapy; 47%
were treated on a single protocol (SJMB 96).
90% of all surviving patients had been seen within 12 months of the analysis.
Sufficient material was available for western blot analysis of ERBB2 protein
expression in 81 tumors and for real-time PCR analysis of TRKC, MYCC and MYCN
RNA expression in 49 tumors.
ERBB2 was scored as positive or negative (relative to control protein).
TRKC, MYCC and MYCN expression were analyzed as categorical variables (based on
expression £ or > the
median value).
All molecular studies were performed blind to clinical outcome.
For analysis of prognostic significance, patients were stratified according to
age at diagnosis (< 3 vs. ³
3 ).
Those ³ 3
were further stratified by standard clinical stage (average-risk vs. high-risk)
and era of therapy (pre vs. post 1996).
The results of stratified comparisons of 5-year progression free survival (PFS)
are shown in the Table.
ERBB2 protein expression was prognostic of PFS in this series of children with
newly diagnosed MB.
Neither TRKC, MYCC nor MYCN expression had prognostic significance although
availability of tumor material restricted the analysis of these molecular
markers. Using these data we are developing a combined clinical and molecular
staging system that will accurately predict disease risk for patients with MB.
Prognostic significance of molecular
markers in medulloblastoma
|
Gene (expression)
|
Number of patients
|
% 5-year PFS (SE)
|
P-value
|
|
ERBB2
(negative)
|
49
|
72(±9)
|
0.017
|
|
ERBB2
(positive)
|
32
|
42(±12)
|
|
|
TRKC
(>1.88)
|
24
|
35(±11)
|
0.55
|
|
TRKC (≤1.88)
|
25
|
52(±13)
|
|
|
MYCC
(>3.69)
|
24
|
47(±14)
|
0.65
|
|
MYCC (≤3.69)
|
25
|
47(±12)
|
|
|
MYCN
(>27.1)
|
24
|
48(±13)
|
0.92
|
|
MYCN (≤27.1)
|
25
|
48(±13)
|
|
© Copyright 2003
American Society of Clinical Oncology All rights
reserved worldwide
Source: http://www.asco.org/ac/1,1003,_12-002489-00_18-002003-00_19-00101997-00_29-00A,00.asp?cat=CNS+Tumors&parent=
Central+Nervous+System+Tumors&returnpid=2325&SubCat_ID=4
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