Increased Inhibitor of Differentiation 4 (Id4) Expression in Glioblastoma: A Tissue Microarray Study
W Zeng, D Hartmann, N Azumi. Georgetown University Hospital, Washington, DC
Background: Inhibitor of differentiation protein family (Id1-4) is involved in negative regulation of helix-loop-helix transcription factors as well as cell cycle control, tumor genesis and angiogenesis. Among these proteins, Id4 is known to have an important role in governing neural stem cell differentiation and increased Id4 mRNA level has been detected in glioblastoma multiforme (GBM) samples and glioma cell lines. Here we report the differential expression of Id4 in astrocytomas of various grades including GBM using tissue microarrays (TMA) and immunohistochemistry (IHC).
Design: The GBM TMA was constructed from 53 cases of archival GBM (grade IV)specimens at Georgetown University Hospital. The normal brain and grade II, III astrocytoma TMA was obtained from Cybrdi (Rockville, MD). TMA sections were stained with Id4 antibody (Chemicon International, Temecula, CA) using a DAKO autoimmunostainer and Envision Flex detection system (DAKO, Carpinteria, CA). The slides were scored according to percentage of the staining nuclei (<9% -, 10-50% +, >51% ++). Fisher Exact test was used to test for statistical significance.
Results: Nuclear staining for Id4 was seen in astrocytoma tumor cells. There was positive staining in 39 of 53 (73.58%) GBMs, 2 of 8 (25%) grade III and 1 of 8 (12.5%) grade II astrocytomas. None of the normal brain tissue (0/16) shows nuclear staining. There was a statistically significant difference between GBM and normal brain tissue, GBM and grade II, III astrocytoma (p <0.01). No statistically significance was detected between normal brain tissue, grade II and grade III astrocytoma (p>0.05).
Conclusions: Our study demonstrates frequent upregulation of Id4 in GBM. The tendency was noted that the higher the grade the more frequent Id4 expression in astrocytomas and none of the normal brain tissue showed positive Id4. This suggests that Id4 overexpression plays an important role in tumorigenesis of astocytomas, possibly in transformation of low to high-grade (i.e. GBM). Further studies of Id4 are warranted to determine its precise role in brain tumorigenesis and its possible use as a target for directed therapy in GBM.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 224, Monday Morning