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Journal of Cancer Research and Clinical Oncology logoLink to Journal of Cancer Research and Clinical Oncology
. 1993 Apr;119(4):185–189. doi: 10.1007/BF01624429

Prognostic implication of immunodetection of P glycoprotein in Ewing's sarcoma

A Roessner 1,, Y Ueda 1, B Bockhorn-Dworniczak 1, S Blasius 1, A Peters 1, P Wuisman 2, J Ritter 3, M Paulussen 3, H Jürgens 3, W Böcker 1
PMCID: PMC12201609  PMID: 8093700

Abstract

Increased expression of P glycoprotein is associated with multidrug resistance in many cell lines. P glycoprotein has been detected in different human tumors. To assess the implication of multidrug resistance in the prognosis of Ewing's sarcoma the expression of P glycoprotein was studied immunohistochemically in pre- and post-therapeutic tumor tissues of 21 cases treated according to the CESS 81 or 86 protocol. The response to chemotherapy was evaluated histologically. Formalin-fixed, paraffin-embedded and fresh frozen sections were immunostained with a monoclonal antibody to P glycoprotein, clone JSB 1, using the double APAAP method. P glycoprotein was detected in 12 cases of 21 (57%) in either pre- or postchemotherapy tumor tissues. From the 21 cases 8 revealed a good morphological response to chemotherapy (33%); 10 of the 13 non-responders were positive for P glycoprotein (77%), but only 2 of the 8 responders (25%). The difference was statistically significant (P<0.05). Comparing P glycoprotein expression with the clinical outcome, we found that 7 of 12 positive cases had died (58%). From the negative cases only 3 of 9 had died (33%). However, judged by the the Kaplan Meyer life tables, these data were not significant. In conclusion our results suggest that the immunodetection of P glycoprotein indicates a poor response to chemotherapy and probably a bad clinical outcome for Ewing's sarcoma patients.

Key words: P glycoprotein, Ewing's sarcoma, Multidrug resistance, Prognosis

Footnotes

Work was supported by the Deutsche Forschungs-Gemeinschaft grant Ro 648/3-1

References

  1. Bates SE, Ching Yi Shieh, Tsokos M (1991) Expression of mdr-1/P-glycoprotein in human neuroblastoma. Am J Pathol 139:305–315 [PMC free article] [PubMed] [Google Scholar]
  2. Bradley G, Juranka PF, Ling V (1988) Mechanism of multidrug resistance. Biochim Biophys Acta 948:87–128 [DOI] [PubMed] [Google Scholar]
  3. Carter RL, Al-Sam SZ, Corbett RP, Clinton S (1990) A comparative study of immunohistochemical staining for neuron-specific enolase, protein gene product 9.5 and S-100 protein in neuroblastoma, Ewing's sarcoma and other round cell tumors in children. Histopathology 16:461–467 [DOI] [PubMed] [Google Scholar]
  4. Chan HSL (1992) Immunohistochemical Detection of P-Glycoprotein in Osteosarcoma. In: Novak JF, McMaster JH (eds) Frontiers in osteosarcoma research. Hogrefe and Huber, Bern (in press) [Google Scholar]
  5. Chan, HSL, Thorner PS, Haddad G, Ling V (1990) Immunohistochemical detection of P-glycoprotein: prognostic correlation in soft tissue sarcoma of childhood. J Clin Oncol 8:689–701 [DOI] [PubMed] [Google Scholar]
  6. Chan HSL, Haddad G, Thorner PS, DeBorger G, Lin YP, Ondrusek N, Yeger H, Ling V (1991) P-glycoprotein expression as a predictor of the outcome of therapy for neuroblastoma. N Engl J Med 325:1608–1614 [DOI] [PubMed] [Google Scholar]
  7. Delling G, Zach W, Alm J (1985) Quantitative Grundsubstanzbestimmung in Osteosarkomen und ihre Bedeutung für das Ansprechen auf eine Polychemotherapie. Verh Dtsch Ges Pathol 69:605 [Google Scholar]
  8. Dietel M (1991) What's new in cytostatic drug resistance and pathology. Pathol Res Pract 187:892–905 [DOI] [PubMed] [Google Scholar]
  9. Endicott JA, Ling V (1989) The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu Rev Biochem 58:137–171 [DOI] [PubMed] [Google Scholar]
  10. Gerlach JH, Endicott JA, Juranka PF, et al. (1986) Homology between P-glycoprotein and a bacterial haemolysin transport protein suggests a model for multidrug resistance. Nature 324:485–489 [DOI] [PubMed] [Google Scholar]
  11. Gottesman MM, Pastan I (1988) The multidrug transporter, a doubleedged sword. J Biol Chem 263:12163–12166 [PubMed] [Google Scholar]
  12. Hijazi Y, Tsokos M, Navarro S, Horowitz M, Axiotis C (1991) Immunohistochemical detection of P-glycoprotein in Ewing's sarcoma and peripheral neuroectodermal tumors (PNET) before and after chemotherapy. Lab Invest 64:5a [DOI] [PubMed] [Google Scholar]
  13. Jürgens H, Exner U, Gadner H, Harms D, Michaelis J, Sauer R, Treuner J, Vautl T, Winkelmann W, Winkler K, Göbel U (1988) Multidisciplinary treatment of Ewing's sarcoma of bone, A 6-year experience of a European cooperative trial. Cancer 61:23–32 [DOI] [PubMed] [Google Scholar]
  14. Kartner N, Evernden-Porelle D, Bradley G, Ling V (1985) Detection of P-glycoprotein in multidrug-resistant cell lines by monoclonal antibodies. Nature 316:820–823 [DOI] [PubMed] [Google Scholar]
  15. Leuschner I, Schmid D, Hoffmann H, Dietel M, Harms D (1991) Expression of P-glycoprotein in soft tissue tumors of childhood. Correlation to treatment response. J Cancer Res Clin Oncol 117
  16. Nooter K, Herweijer H (1991) Multidrug resistance (mdr) genes in human cancer. Br J Cancer 63:663–669 [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pastan I, Gottesman MM (1987) Multiple-drug resistance in human cancer. N Engl J Med 316:1388–1393 [DOI] [PubMed] [Google Scholar]
  18. Riordan JR, Deuchars K, Kartner N, Alon N, Trent J, Ling V (1985) Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines. Nature 316:817–819 [DOI] [PubMed] [Google Scholar]
  19. Robery-Cafferty SS, Rutledge ML, Bruner JM (1990) Expression of a multidrug resistant gene in esophageal adenocarcinoma. Correlation with response to chemotherapy and comparison with gastric adenocarcinoma. Am J Clin Pathol 93:1–7 [DOI] [PubMed] [Google Scholar]
  20. Roessner A, Ueda Y, Bockhorn-Dworniczak B, Vollmer E, Edel G, Mellin W, Blasius S, Wuisman P, Böcker W, Grundmann E (1992a) Current aspects of cell biology in osteosarcoma. In: Novak JF, McMaster JH (eds) Frontiers in osteosarcoma research. Hogrefe and Huber, Bern (in press) [Google Scholar]
  21. Roessner A, Ueda Y, Bockhorn-Dworniczak B, Blasius S, Edel G, Barwinkel F, Wuisman D., Jürgens H, Böcker W (1992) Zur klinischen Bedeutung des p-Glykoproteinnachweises in menschlichen Osteosarkomen. Verh Dtsch Ges Path 76 Tg. (in press)
  22. Roninson IB, Chin JE, Choi K et al. (1986) Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells. Proc Natl Acad Sci USA 83:4538–4542 [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Salzer-Kuntschik M, Delling G, Beron G, Sigmund R (1983) Bestimmung des morphologischen Regressionsgrades nach Chemotherapie bei malignen Knochentumoren. Pathologe 4:135–141 [PubMed] [Google Scholar]
  24. Scheper RJ, Multe JWM, Brakkee JGP, Quak JJ, Schoot E van der, Balm AJM, Meijer CJLM, Broxterman HJ, Kuiper CM, Lankelma J, Pinedo HM (1988) Monoclonal antibody JSB-1 detects a highly conserved epitope on the P-glycoprotein associated with multidrug-resistance. Int J Cancer 42:389–394 [DOI] [PubMed] [Google Scholar]
  25. Schmidt D, Herrmann CH, Jürgens H, Harms D (1991) Malignant peripheral neuroectodermal tumor and its necessary distinction from Ewing's sarcoma. A report from the Kiel Pediatric Tumor Registry. Cancer 68:2251–2259 [DOI] [PubMed] [Google Scholar]
  26. Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, Willingham MC (1987) Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci USA 84:7735–7738 [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Triche T, Cavazzana A (1988) Round cell tumors of bone. In: Unni KK (ed) Bone tumors. Churchill Livingstone. New York, pp 183–198 [Google Scholar]
  28. Weinstein RS, Kuszak JR, Kluskens LF, Coon JS (1990) P-glycoproteins in pathology: the multidrug resistance gene family in humans. Hum Pathol 21:34–48 [DOI] [PubMed] [Google Scholar]

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