Summary
1. Cellular expression and distribution of the stress response small heat shock protein 27 (hsp27) in 39 high-grade astrocytomas (27 glioblastoma multiformes, 12 anaplastic astrocytomas) and in 27 low-grade astrocytomas (grade I–II) were analyzed immunohistochemically.
2. The correlation between hsp27 expression and tumor growth fractions of the astrocytomas was examined following Ki-67 immunostaining.
3. The hsp27 staining was cell cytoplasmic. The hsp27 immunopositive rate was significantly higher in high-grade astrocytomas; the rates were 74% for glioblastomas, 58% for anaplastic astrocytomas, and 37% for low-grade astrocytomas. The small and large tumor cells, especially in glioblastomas, multinucleated tumor giant cells, tumor cells in the pseudopalisading and necrotic areas, cells of the microvascular endothelial proliferations, and tumor vascular smooth muscles were usually hsp27 positive. The mean percentage of hsp27-positive cells was significantly higher in the glioblastomas alone and in the combined high-grade astrocytomas, compared to the low-grade, and in recurrent rather than in primary high-grade astrocytomas.
4. The high-grade astrocytomas had a highly statistical significant Ki-67 labeling index. The Ki-67 labeling indices were significantly higher in the hsp27-positive than the hsp27-negative astrocytomas, irrespective of the histological grade. In the high-grade astrocytomas with a Ki-67 labeling index of five and above, 81% of those tumors were hsp27 positive.
5. Thus, a large number of human astrocytomas express hsp27, and hsp27 expression correlates with histological grades of astrocytoma and with tumor growth fractions. This being the case, hsp27 is likely to have a role in the growth of human astrocytomas.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Arrigo, A. P., Suhan, J. P., and Welch, W. J. (1988). Dynamic changes in the structure and intracellular locale of the mammalian low-molecular-weight heat shock protein.Mol. Cell. Biol. 85059–5071.
Chambard, J. C., Franchi, A., Cam, A. L., and Poayssegur, J. (1983). Growth factor-stimulated protein phosphorylation in GO/G1-arrested fibroblast. Two distinct classes of growth factors with potentiating effects.J. Biol. Chem. 2581706–1713.
Chamness, G. C., Ruiz, A., Fulcher, L., Clark, G., Fuqua, S., and McGuire, W. (1989). Estrogen-inducible heat shock protein hsp27 predicts recurrence in node-negative breast cancer.Proc. Am. Assoc. Cancer Res. 30252.
Chirico, W. J., Waters, M. G., and Blobet, G. (1988). 70 KD heat shock regulated proteins stimulate protein translocation into microsomes.Nature 322805–810.
Darbon, J. M., Tournier, J. F., Tauber, J. P., and Bayard, F. (1986). Possible role of protein phosphorylation in the mitogenic effect of high density lipoproteins on cultured vascular endothelial cells.J. Biol. Chem. 2618002–8008.
Darbon, J. M., Issandou, M., Tournier, J. F., and Bayard, F. (1990). The respective 27 KDa and 28 KDa protein kinase C substrates in vascular endothelial and MCF-7 cells are most probably heat shock proteins.Biochem. Biophys. Res. Commun. 168527–536.
Deshaies, R. J., Koch, B. D., Washburne, M. W., Craig, E. A., and Schekman, R. (1988). A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptide.Nature 332800–805.
Ellis, R. J., and Van der Vies, S. M. (1991). Molecular chaperones.Annu. Rev. Biochem. 60321–347.
Fleming, T. P., Saxena, A., Clark, W. C., Robertson, J. T., Oldfield, E. H., Aaronson, S. A., and Ali, I. V. (1992). Amplification and/or overexpression of platelet-derived growth factor receptors and epidermal growth factor receptor in human glial tumors.Cancer Res. 524550–4553.
Fuqua, S. A. W., Blun-Salingaros, M., and McGuire, W. L. (1989). Induction of the estrogen-regulated “24 K” protein by heat shock.Cancer Res. 44126–4129.
Hepburn, A., Demolle, D., Boeynaems, J. M., Fiers, W., and Dumont, J. E. (1988). Rapid phosphorylation of a 27 KDa protein induced by tumor necrosis factor.FEBS Lett. 227175–178.
Kato, M., Hertz, F., Kato, S., and Hirano, A. (1992). Expression of stress-response (heat-shock) protein 27 in human brain tumors: An immunohistochemical study.Acta Neuropathol. 83420–422.
Kato, S., Hirano, A., Kato, M., Herz, F., and Ohama, E. (1993). Comparative study on the expression of stress-response protein (sr)p 72, srp27, alpha B-crystallin and ubiquitin in brain tumors: An immunohistochemical investigation.Neuropathol. Appl. Neurobiol. 19436–442.
Kaur, P., and Saklatvala, J. (1988). Interleukin-1 and tumor necrosis factor increases phosphorylation of fibroblast proteins.FEBS Lett. 2416–10.
Key, J. L., Lin, C. Y., and Chen, Y. M. (1981). Heat shock proteins of higher plants.Proc. Natl. Acad. Sci. USA 781708–1711.
Landry, J., Chretien, P., Lambert, H., Hickey, E., and Weber, L. A. (1989). Heat shock resistance conferred by expression of the human Hsp27 gene in rodent cells.J. Cell Biol. 1097–15.
Manley, J. L., Fire, A., Samuel, M., and Sharp, P. A. (1983). In vitro transcription: Whole cell extract.Methods Enzymol. 101568–582.
McGuire, S. E., Fuqua, S. A. W., and Naylor, S. L. (1989). Chromosomal assignments of human 27-KDa heat shock protein gene family.Somat. Cell. Mol. Genet. 15167–171.
Michishita, M., Satoh, M., Yamaguchi, M., Hirayoshi, K., Okuma, M., and Nagata, K. (1991). Phosphorylation of the stress protein Hsp27 is an early event in murine myelomonocytic leukemia cell differentiation induced by leukemia inhibitory factor/D-factor.Biochem. Biophys. Res. Commun. 176979–984.
Montine, T. J., Vandersteenhoven, J. J., Aguzzi, A., Boyko, O. B., Dodge, R. K., Kerns, B. J., and Burger, P. C. (1994). Prognostic significance of Ki-67 proliferation index in supratentorial fibrillary astrocytic neoplasm.Neurosurgery 34674–679.
Morimoto, R. I. (1991). Heat shock: The role of transient inducible responses in cell damage, tranformation, and differentiation.Cancer Res. 3295–301.
Pecham, P.M. (1991). Heat shock proteins and cell proliferation.FEBS Lett. 2801–4.
Raghavan, R., Steart, P., and Weller, R. O. (1990). Cell proliferation patterns in the diagnosis of astrocytomas, anaplastic astrocytomas, and glioblastoma multiforme. A Ki-67 study.Neuropathol. Appl. Neurobiol. 16123–133.
Rasheed, B. K. A., McLendon, R. E., Herndon, J. E., Friedman, H. S., Friedman, A. H., Bigner, D. D., and Bigner, S. H. (1994). Alterations of the TP53 gene in human gliomas.Cancer Res. 541324–1330.
Renkawek, K., Bosman, G. J. C. M., and de Jong, W. W. (1994). Expression of small heat-shock protein hsp27 in reactive gliosis in Alzheimer disease and other types of dementia.Acta Neuropathol. 87511–519.
Sahai, A., Feuerstein, N., Cooper, H. L., and Salomon, D. S. (1986). Effect of epidermal growth factor and 12-O-tetradecanoylphorbol-13-acetate on the phosphorylation of soluble acidic proteins in A431 epidermoid carcinoma cells.Cancer Res. 464143–4150.
Shibuya, M., Ito, S., Miwa, T., Davis, R. L., Wilson, C. B., and Hoshino, T. (1993). Proliferative potential of brain tumors.Cancer 71199–206.
Thor, A., Benz, C., Moore, D. II., Goldman, E., Edgerton, S., Landry, J., Schwartz, L., Mayall, B., Hickey, E., and Weber, L. A. (1991). Stress response protein (srp-27) determination in primary human breast carcinomas: Clinical, histologic, and prognostic correlations.J. Natl. Cancer Inst. 83170–178.
Yokoyama, N., Iwaki, T., Goldman, J. E., Tateishi, J., and Fukui, M. (1993). Small heat-shock protein is expressed in meningiomas and in granulofilamentous inclusion bodies.Acta Neuropathol. 85248–255.
Zulch, K. J. (1979).International Histological Classification of Tumors, No. 21, World Health Organization, Geneva.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Khalid, H., Tsutsumi, K., Yamashita, H. et al. Expression of the small heat shock protein (hsp) 27 in human astrocytomas correlates with histologic grades and tumor growth fractions. Cell Mol Neurobiol 15, 257–268 (1995). https://doi.org/10.1007/BF02073332
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02073332