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 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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