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

Abstract

Summary 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 fixationsensitive 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.

Expression of MDR1/P glycoprotein in human sarcomas

“…We did not observe any heterogeneity of MDR1 expression by ISH in these sarcomas. This rules out the negative results of the DB hybridisation method being (Thiebaut et al, 1987;Sugawara et al, 1988;Cordon Cardo et al, 1990;Schlaifer et al, 1990;Van der Valk et al, 1990 the P-gp, and then to confirm positive results with a method such as ISH which detects MDR1 mRNA expression.…”

Mdr1/P-glycoprotein, topoisomerase, and glutathione-S-transferase π gene expression in primary and relapsed state adult and childhood leukaemias

“…The monoclonal antibody C219 was used for examination of leukaemia cell samples by others as well (Ma et al, 1987;Volm et al, 1989;Musto et al, 1990;Schlaifer et al, 1990). Some limitations using this reagent have to be considered, though.…”

Evaluation of flow cytometry for multidrug resistance detection in low resistance K562 cells using daunorubicin and monoclonal antibodies

“…In the past, use of C219 has been proven to be reliable in different techniques for the demonstration of Pgp overproduction in clinical samples (7,10,11,29,33,34). Hence, this probe can still be used in seeking a role for Pgp in drug resistance in vivo (11,21).…”