[1674] Heat Shock Protein (HSP) Expression in Diffuse Gliomas: A Potential Therapeutic Target

A Gonzalez, R Kolhe, S Sharma. Medical College of Georgia, Augusta, GA

Background: HSPs are molecular chaperones which facilitate tumor growth and resistance to radiation/chemotherapy. HSP90 antagonists are being pursued in therapeutic trials. Scant data is available in diffuse gliomas (DG). We evaluated the expression of HSP27, 70 and 90 in DGs.
Design: Representative paraffin blocks from 17 diffuse gliomas: 5 astrocytomas grade-II (A), 5 anaplastic astrocytomas (AA), 3 glioblastomas (GBM), 1 glioblastoma-oligodendroglioma type (GBM-O), and 3 oligodendroglioma grade-II (OG), were immunostained with antibodies to HSP27, 70 and 90. Percentage positivity of neoplastic cells was evaluated (less than 10% considered negative). Expression of HSPs was validated on endometrium and internal vascular controls.
Results: The immunoreactivity was cytoplasmic. The percentage of positive cases is tabulated. Among astrocytic tumors, HSP27 expression was more pronounced in GBM, and in larger/pleomorphic or gemistocytic cells in all 3 grades. In contrast, HSP70 and HSP90 showed positivity mainly in small/intermediate sized neoplastic cells. In GBM, 2 cases showed peri-necrotic and 1 perivascular accentuation. Hyperplastic vessels were highlighted in 1 GBM. Among oligodendroglial tumors, HSP 70 and 90 were positive in 2 and 1 cases respectively, whereas HSP27 was reciprocally positive in GBM-O and one grade II OG with increased Ki67 labeling. The mean value of HSP27 percentage positivity of tumor cells was higher in high-grade as compared to low-grade diffuse gliomas, most pronounced in GBM as well as GBM-O (see table).

HSP Stain Distribution in High-grade diffuse gliomas

Tumor Type	HSP27 + cases	Mean % positive tumor cells	HSP70 + cases	Mean % positive tumor cells	HSP90 + cases	Mean % positive tumor cells
AA (5)	3	32	5	52	5	57
GBM (3)	3	58	3	65	3	45
GBM-O (1)	1	90	0	0	0	0
Total = 9	7 (77%)	60	8 (88%)	39	8 (88%)	34

HSP Stain Distribution in Low-grade diffuse gliomas

Tumor Type	HSP27 + cases	Mean % positive tumor cells	HSP70 + cases	Mean % positive tumor cells	HSP90 + cases	Mean % positive tumor cells
A (5)	3	36	5	60	5	52
OG (3)	1	8	2	36	1	20
Total = 8	4 (50%)	22	7 (87%)	48	6 (75%)	36

Conclusions: HSP27, 70 and 90 are expressed in diffuse gliomas. HSP27 showed increased expression in GBM, in larger/gemistocytic cells, and among low-grade astrocytic compared to oligodendroglial tumors. This expression pattern of HSPs suggests their role in the growth of diffuse gliomas, and as potential therapeutic targets in high-grade gliomas.
Category: Neuropathology

Tuesday, March 23, 2010 1:00 PM

Poster Session IV # 227, Tuesday Afternoon