P-glycoprotein expression in primary and metastatic transitional cell carcinoma of the bladder. Academic Article uri icon

Overview

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 immunohistochemical technique. Immunoreactivity was scored separately in tumor cells and endothelial cells. RESULTS: Untreated primary lesions showed immunostaining 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 positivity for p-glycoprotein (p = 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.

publication date

  • November 1, 1994

Research

keywords

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Combined Chemotherapy Protocols
  • Carcinoma, Transitional Cell
  • Urinary Bladder Neoplasms

Identity

Scopus Document Identifier

  • 0028061548

Digital Object Identifier (DOI)

  • 10.1093/oxfordjournals.annonc.a059013

PubMed ID

  • 7848886

Additional Document Info

volume

  • 5

issue

  • 9