Abstract
Expression of the glutathioneS-transferase (GST) subclasses α, μ and π was investigated immunohistochemically in 20 normal or hyperplastic mesothelium and in 57 malignant mesothelioma cases. These results were correlated with survival and also with P-170 glycoprotein expression. Nearly all the non-neoplastic mesothelium cases were positive for GSTα and π. About half of the non-neoplastic cases were positive for μ. Twenty-nine (51%) malignant mesotheliomas were positive for at least one of the GST species; 21 (37%) showed immunoreactivity for α, 18 (31.5%) for μ and 21 (37%) for π. A total of 54 mesothelioma cases displayed immunoreactivity for the P-170 glycoprotein. For GSTπ and GSTμ, a statistical significance between expression and increased survival was found (respectivelyP=0.012 and 0.024) while for GSTα no significance was found. The results of this study demonstrate that expression of GSTπ correlates positively with increased survival in malignant mesothelioma. It is also concluded that, in mesothelioma, GST and P-170 glycoprotein may contribute to the resistance to cytotoxic drugs frequently observed in these tumours. No correlation between GST and P-170 expression was demonstrated.
Similar content being viewed by others
Abbreviations
- GST :
-
glutathioneS-transferase
References
Aisner J (1995) Current approach to malignant mesothelioma of the pleura. Chest 107:332S-344S
Ali-Osman F, Stein DE, Renwick A (1990) Glutathione content and glutathione-S-transferase expression in 1,3-bis(2-chloroethyl)-1-nitrosourea resistant human malignant astrocytoma cell lines. Cancer Res 50:6976–6980
Bellamy CO, Harrison DJ (1994) Evaluation of glutathioneS-transferase Pi in non-invasive ductal carcinoma of breast. Br J Cancer 69:183–185
Board PG, Coggan M (1989)BamHI andEcoRI restriction fragment length polymorphisms at the glutathioneS-transferase 3 locus. Nucleic Acids Res 17:7550
Butchart EJ, Ashcroft T, Barnsley WC, Holden MP (1976) Pleural pneumectomy in the management of diffuse malignant mesothelioma. Thorax 31:15–24
Cairns J, Wright C, Cattan AR, Hall AG, Cantwell BJ, Harris AL, Horne CH (1992) Immunohistochemical demonstration of glutathioneS-transferases in primary human breast carcinomas. J Pathol 166:19–25
Campbell JA, Corrigall AV, Guy A, Kirsch RE (1991) Immunohistologic localization of alpha, mu, and pi class glutathioneS-transferases in human tissues. Cancer 67:1608–1613
Coles B, Ketterer B (1990) The role of glutathione and glutathione transferases in chemical carcinogenesis. Crit Rev Biochem Mol Biol 25:47–70
Collier JD, Bennett MK, Hall A, Cattan AR, Lendrum R, Bassendine MF (1994) Expression of glutathioneS-transferases in normal and malignant pancreas: an immunohistochemical study. Gut 35:266–269
Efferth T, Mattern J, Volm M (1992) Immunohistochemical detection of P glycoprotein, glutathioneS-transferase and DNA topoisomerase II in human tumors. Oncology 49:368–375
Gilbert L, Elwood LJ, Merino M, Masood S, Barnes R, Steinberg SM, Lazarous DF, Pierce L, d'Angelo T, Moscow JA (1993) A pilot study of pi-class glutathioneS-transferase expression in breast cancer: correlation with estrogen receptor expression and prognosis in node-negative breast cancer. J Clin Oncol 11:49–58
Gottesman MM, Pastan I (1993) Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem 62:385–427
Green JA, Robertson LJ, Clark AH (1993) GlutathioneS-transferase expression in benign and malignant ovarian tumours. Br J Cancer 68:235–239
Habig WH, Jakoby WB (1981) GlutathioneS-transferases (rat and human). Methods Enzymol 77:218–231
Hall A, Foster S, Proctor SJ, Cattan AR (1990) Purification and characterization of a pi class glutathioneS-transferase from human leukaemic cells. Br J Haematol 76:494–500
Hamada S, Kamada M, Furumoto H, Hirao T, Aono T (1994) Expression of glutathioneS-transferase-pi in human ovarian cancer as an indicator of resistanceto chemotherapy. Gynecol Oncol 52:313–319
Hayes PC, May L, Hayes JD, Harrison DJ (1991) GlutathioneS-transferases in human liver cancer. Gut 32:1546–1549
Hirvonen A, Pelin K, Tammilehto L, Karjalainen A, Mattson K, Linnainmaa K (1995) InheritedGSTM1 andNAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma. Cancer Res 55:2981–2983
Isobe H, Wellham L, Sauerteig A, Sridhar KS, Ramachandran C, Krishan A (1994) Doxorubicin retention and chemoresistance in human mesothelioma cell lines. Int J Cancer 57:581–585
Kantor RR, Giardina SL, Bartolazzi A, Townsend AJ, Myers CE, Cowan KH, Longo DL, Natali PG (1991) Monoclonal antibodies to glutathioneS-transferase pi-immunohistochemical analysis of human tissues and cancers. Int J Cancer 47:193–201
Katagiri A, Tomita Y, Nishiyama T, Kimura M, Sato S (1993) Immunohistochemical detection of P-glycoprotein and GSTP1-1 in testis cancer. Br J Cancer 68:125–129
Laisney V, Nguyen Van Cong, Gross MS, Frezal J (1984) Human genes for glutathioneS-transferases. Hum Genet 68:221–227
Mannervik B, Guthenberg C (1985) Glutathione transferase (human placenta). Methods Enzymol 77:231–235
Mannervik B, Alin P, Guthenberg C, Jensson H, Tahir MK, Warholm M, Jornvall H (1985) Indentification of three classes of cytosolic glutathione transferase common to several mammalian species:correlation between structural data and enzymatic properties. Proc Natl Acad Sci USA 82:7202–7206
McKay JA, Murray GI, Ewen WB, Melvin WT, Burke MD (1994) Immunohistochemical localization of glutathioneS-transferases in sarcomas. J Pathol 174:83–87
Morgenstem R, DePierre JW (1983) Microsomal glutathione transferase. Purification in unactivated form and further characterization of the activation process, substrate specificity and amino acid composition. Eur J Biochem 134:591–597
Peters WH, Roelofs HM, Putten WI van, Jansen JB, Klijn JG, Foekens JA (1993) Response to adjuvant chemotherapy in primary breast cancer: no correlation with expression of glutathioneS-transferases. Br J Cancer 63:86–92
Ramael M, Bossche J van den, Buysse C, Meerbeeck J van, Segers K, Vermeire P, Marck E van (1992) Immunoreactivity for P-170 glycoprotein in malignant mesothelioma and in non-neoplastic mesothelium of the pleura using the murine monoclonal antibody JSB-1. J Pathol 167:5–8
Robson CN, Lewis AD, Wolf CR, Hayes JD, Hall A, Proctor SJ, Harris AL, Hickson ID (1987) Reduced levels of drug-induced DNA cross-linking in nitrogen mustard-resistant Chinese hamster ovary cells expressing elevated glutathioneS-transferase activity. Cancer Res 47:6022–6027
Scheper RJ, Bulte JW, Brakkee JG, Quak JJ, Schoot E van der, Balm AJ, Meijer CJ, Broxterman HJ, Kuiper CM, Lankelma J (1988) Monoclonal antibody JSB-1 detects a highly conserved epitope on the P-glycoprotein associated with multi-drug-resistance. Int J Cancer 42:389–394
Tsuchida S, Sekine Y, Shineha R, Nishihira T, Sato K (1989) Elevation of the placental glutathioneS-transferase form (GST-pi) in tumor tissues and the levels in sera of patients with cancer. Cancer Res 49:5225–5229
Van Meerbeeck JP (1994) Prognostic factors in malignant mesothelioma: where do we go from here? Eur Respir J 7:1029–1031
Volm M, Mattern J, Samsel B (1991) Overexpression of P-glycoprotein and glutathioneS-transferase-π in resistant non-small cell lung carcinomas of smokers. Br J Cancer 64:700–704
Volm M, Kastel M, Mattern J, Efferth T (1993) Expression of resistance factors (P-glycoprotein, glutathioneS-transferase-pi, and topoisomerase II) and their interrelationship to protooncogene products in renal cell carcinomas. Cancer 71: 3981–3987
Weinstein RS, Kuszak JR, Jakate SM, Lebovitz MD, Kluskens LF, Coon JS (1990) ABO blood type predicts the cytolocalization of anti-P-glycoprotein monoclonal antibody reactivity in human colon and ureter. Hum Pathol 21:949–958
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Segers, K., Kumar-Singh, S., Weyler, J. et al. GlutathioneS-transferase expression in malignant mesothelioma and non-neoplastic mesothelium: an immunohistochemical study. J Cancer Res Clin Oncol 122, 619–624 (1996). https://doi.org/10.1007/BF01221194
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01221194