P-glycoprotein expression in primary and metastatic transitional cell carcinoma of the bladder Journal Article

Authors: Petrylak, D. P.; Scher, H. I.; Reuter, V.; O'Brien, J. P.; Cordon-Cardo, C.
Article Title: P-glycoprotein expression in primary and metastatic transitional cell carcinoma of the bladder
Abstract: Background: To determine the expression of P-glycoprotein in pre- and post-chemotherapy tumor tissue samples from patients with transitional cell carcinomas treated with M-VAC (methotrexate, vinblastine, adriamycin and cisplatin). Patients and methods: Fresh frozen tissue sections of primary and metastatic urothelial tumors were stained with mouse monoclonal antibody HYB-241 which recognized an external epitope of P-glycoprotein, using an avidin-biotin im-munohistochemical technique. Immunoreactivity was scored separately in tumor cells and endothelial cells. Results: Untreated primary lesions showed immunostain-ing in 6 of 46 cases (13%), while 6 of 16 (38%) post-therapy primary tumors were immunoreactive. None of the untreated metastases (0 of 17) were positive, however, 6 of 11 (55%) post-therapy specimens showed varied percentages of posi-tivity for p-glycoprotein (p {box drawings light horizontal} 0.002). The highest percentage, 50%-70% of tumor cells stained, was observed in metastatic lesions from patients who had received 6 or more chemotherapy cycles. No difference in the proportion of endothelial cells stained was observed in pre- and post-therapy specimens. However, 3 of 6 post-therapy samples obtained from 5 individual patients showed MDR1 up-regulation on endothelial cells. Conclusions: The data show that an increase in the proportion of cells expressing P-glycoprotein occurs after exposure to a combination chemotherapy program containing drugs known to select for P-glycoprotein expression in vitro. The observation of increased immunoreactive endothelial cells suggests transactivation of the MDR1 in these cells. While data are preliminary, P-glycoprotein expression in capillary endothelial cells may contribute to drug resistance. Taken together, these mechanisms may contribute to therapeutic failure in patients with bladder tumors treated with chemotherapy. © 1994 Kluwer Academic Publishers.
Keywords: immunohistochemistry; clinical article; human tissue; cisplatin; doxorubicin; methotrexate; antigen expression; metastasis; drug resistance; bladder cancer; vinblastine; transitional cell carcinoma; p-glycoprotein; glycoprotein p; mdr; urothelial tumors; m-vac; human; priority journal; article
Journal Title: Annals of Oncology
Volume: 5
Issue: 9
ISSN: 0923-7534
Publisher: Oxford University Press  
Date Published: 1994-11-01
Start Page: 835
End Page: 840
Language: English
PROVIDER: scopus
PUBMED: 7848886
DOI: 10.1093/oxfordjournals.annonc.a059013
Notes: Export Date: 14 January 2019 -- Article -- Source: Scopus
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MSK Authors
  1. James O'Brien
    19 O'Brien
  2. Victor Reuter
    978 Reuter
  3. Howard Scher
    884 Scher