Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1990 Aug;62(2):177–182. doi: 10.1038/bjc.1990.256

Immunohistochemical detection of multidrug resistance associated P-glycoprotein in tumour and stromal cells of human cancers.

D Schlaifer 1, G Laurent 1, S Chittal 1, T Tsuruo 1, S Soues 1, C Muller 1, J Y Charcosset 1, C Alard 1, P Brousset 1, C Mazerrolles 1, et al.
PMCID: PMC1971839  PMID: 1974813

Abstract

The distribution of Gp 170, a multidrug resistance (MDR) associated glycoprotein, also called P-glycoprotein (P-gp), was examined by immunohistochemistry, using C219 and MRK16 monoclonal antibodies. Sixty-five tumour tissues were studied which included 40 non-lymphoid tumours, 15 chemoresistant non-Hodgkin's lymphomas and 10 Hodgkin's disease. The study was performed on both cryostat and special fixation processed and paraplast embedded (ModAMeX) sections. The latter method preserves fixation-sensitive antigens such as P-gp and allows a more precise morphological identification of neoplastic and non-neoplastic cell populations in contrast to cryostat sections. Immunohistochemical expression of P-gp was expected and confirmed in many non-lymphoid tumours, but stromal macrophages and endothelial cells were also frequently stained in these cases. In non-Hodgkin's lymphomas, cells that were stained with both C219 and MRK16 monoclonal antibodies on cryostat sections were identified as macrophages and endothelial cells and not neoplastic lymphoid cells, by the ModAMeX technique. These findings suggest that the quantitative assessment of MDR RNA by Northern blotting performed on fresh homogenates overestimates the MDR content of neoplastic cells in a number of lymphoid and non-lymphoid tumours. In addition, the mechanism of chemoresistance in non-Hodgkin's lymphomas is less likely to be associated with P-gp expression.

Full text

PDF
177

Images in this article

180Figure 1
on p.180
180Figure 2
on p.180

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bell D. R., Gerlach J. H., Kartner N., Buick R. N., Ling V. Detection of P-glycoprotein in ovarian cancer: a molecular marker associated with multidrug resistance. J Clin Oncol. 1985 Mar;3(3):311–315. doi: 10.1200/JCO.1985.3.3.311. [DOI] [PubMed] [Google Scholar]
  2. Bradley G., Juranka P. F., Ling V. Mechanism of multidrug resistance. Biochim Biophys Acta. 1988 Aug 3;948(1):87–128. doi: 10.1016/0304-419x(88)90006-6. [DOI] [PubMed] [Google Scholar]
  3. Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
  4. Dalton W. S., Grogan T. M., Meltzer P. S., Scheper R. J., Durie B. G., Taylor C. W., Miller T. P., Salmon S. E. Drug-resistance in multiple myeloma and non-Hodgkin's lymphoma: detection of P-glycoprotein and potential circumvention by addition of verapamil to chemotherapy. J Clin Oncol. 1989 Apr;7(4):415–424. doi: 10.1200/JCO.1989.7.4.415. [DOI] [PubMed] [Google Scholar]
  5. Delsol G., Chittal S., Brousset P., Caveriviere P., Roda D., Mazerolles C., Barillet-Alard C., al Saati T., Gorguet B., Voigt J. J. Immunohistochemical demonstration of leucocyte differentiation antigens on paraffin sections using a modified AMeX (ModAMeX) method. Histopathology. 1989 Nov;15(5):461–471. doi: 10.1111/j.1365-2559.1989.tb01606.x. [DOI] [PubMed] [Google Scholar]
  6. Fojo A. T., Shen D. W., Mickley L. A., Pastan I., Gottesman M. M. Intrinsic drug resistance in human kidney cancer is associated with expression of a human multidrug-resistance gene. J Clin Oncol. 1987 Dec;5(12):1922–1927. doi: 10.1200/JCO.1987.5.12.1922. [DOI] [PubMed] [Google Scholar]
  7. Fojo A. T., Ueda K., Slamon D. J., Poplack D. G., Gottesman M. M., Pastan I. Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci U S A. 1987 Jan;84(1):265–269. doi: 10.1073/pnas.84.1.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gerlach J. H., Bell D. R., Karakousis C., Slocum H. K., Kartner N., Rustum Y. M., Ling V., Baker R. M. P-glycoprotein in human sarcoma: evidence for multidrug resistance. J Clin Oncol. 1987 Sep;5(9):1452–1460. doi: 10.1200/JCO.1987.5.9.1452. [DOI] [PubMed] [Google Scholar]
  9. Goldstein L. J., Galski H., Fojo A., Willingham M., Lai S. L., Gazdar A., Pirker R., Green A., Crist W., Brodeur G. M. Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst. 1989 Jan 18;81(2):116–124. doi: 10.1093/jnci/81.2.116. [DOI] [PubMed] [Google Scholar]
  10. Hamada H., Tsuruo T. Functional role for the 170- to 180-kDa glycoprotein specific to drug-resistant tumor cells as revealed by monoclonal antibodies. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7785–7789. doi: 10.1073/pnas.83.20.7785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kartner N., Evernden-Porelle D., Bradley G., Ling V. Detection of P-glycoprotein in multidrug-resistant cell lines by monoclonal antibodies. 1985 Aug 29-Sep 4Nature. 316(6031):820–823. doi: 10.1038/316820a0. [DOI] [PubMed] [Google Scholar]
  12. Kaye S. B. The multidrug resistance phenotype. Br J Cancer. 1988 Dec;58(6):691–694. doi: 10.1038/bjc.1988.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Laurent G., Al Saati T., Olive D., Laurent J. C., Poncelet P., Delsol G. Expression of Tac antigen in B cell lymphomas. Clin Exp Immunol. 1986 Aug;65(2):354–362. [PMC free article] [PubMed] [Google Scholar]
  14. Moscow J. A., Fairchild C. R., Madden M. J., Ransom D. T., Wieand H. S., O'Brien E. E., Poplack D. G., Cossman J., Myers C. E., Cowan K. H. Expression of anionic glutathione-S-transferase and P-glycoprotein genes in human tissues and tumors. Cancer Res. 1989 Mar 15;49(6):1422–1428. [PubMed] [Google Scholar]
  15. Pastan I., Gottesman M. Multiple-drug resistance in human cancer. N Engl J Med. 1987 May 28;316(22):1388–1393. doi: 10.1056/NEJM198705283162207. [DOI] [PubMed] [Google Scholar]
  16. Salmon S. E., Grogan T. M., Miller T., Scheper R., Dalton W. S. Prediction of doxorubicin resistance in vitro in myeloma, lymphoma, and breast cancer by P-glycoprotein staining. J Natl Cancer Inst. 1989 May 3;81(9):696–701. doi: 10.1093/jnci/81.9.696. [DOI] [PubMed] [Google Scholar]
  17. Sato Y., Mukai K., Watanabe S., Goto M., Shimosato Y. The AMeX method. A simplified technique of tissue processing and paraffin embedding with improved preservation of antigens for immunostaining. Am J Pathol. 1986 Dec;125(3):431–435. [PMC free article] [PubMed] [Google Scholar]
  18. Scheper R. J., Bulte J. W., Brakkee J. G., Quak J. J., van der Schoot E., Balm A. J., Meijer C. J., Broxterman H. J., Kuiper C. M., Lankelma J. Monoclonal antibody JSB-1 detects a highly conserved epitope on the P-glycoprotein associated with multi-drug-resistance. Int J Cancer. 1988 Sep 15;42(3):389–394. doi: 10.1002/ijc.2910420314. [DOI] [PubMed] [Google Scholar]
  19. Shen D. W., Pastan I., Gottesman M. M. In situ hybridization analysis of acquisition and loss of the human multidrug-resistance gene. Cancer Res. 1988 Aug 1;48(15):4334–4339. [PubMed] [Google Scholar]
  20. Sugawara I., Kataoka I., Morishita Y., Hamada H., Tsuruo T., Itoyama S., Mori S. Tissue distribution of P-glycoprotein encoded by a multidrug-resistant gene as revealed by a monoclonal antibody, MRK 16. Cancer Res. 1988 Apr 1;48(7):1926–1929. [PubMed] [Google Scholar]
  21. Sugawara I., Kodo H., Ohkochi E., Hamada H., Tsuruo T., Mori S. High-level expression of MRK 16 and MRK 20 murine monoclonal antibody-define proteins (170,000-180,000 P-glycoprotein and 85,000 protein) in leukaemias and malignant lymphomas. Br J Cancer. 1989 Oct;60(4):538–541. doi: 10.1038/bjc.1989.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Thiebaut F., Tsuruo T., Hamada H., Gottesman M. M., Pastan I., Willingham M. C. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7735–7738. doi: 10.1073/pnas.84.21.7735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Thiebaut F., Tsuruo T., Hamada H., Gottesman M. M., Pastan I., Willingham M. C. Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: evidence for localization in brain capillaries and crossreactivity of one antibody with a muscle protein. J Histochem Cytochem. 1989 Feb;37(2):159–164. doi: 10.1177/37.2.2463300. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES