Prognostic relevance of P-glycoprotein expression in breast cancer

S. C. Linn, G. Giaccone, P. J. Van Diest, W. M D Blokhuis, P. Van Der Valk, C. K. Van Kalken, C. M. Kuiper, H. M. Pinedo, J. P A Baak

Research output: Contribution to journalArticlepeer-review

Abstract

Background: P-glycoprotein (Pgp) expression has been reported to be associated with a poor prognosis in some malignancies such as neuroblastoma, soft tissue sarcoma and acute myeloid leukemia. The prognostic role of Pgp expression in breast cancer is still unclear. We investigated the expression of Pgp in primary and metastatic breast cancer tissues in relation to patient characteristics and treatment outcome. Patients and methods: Pgp expression was evaluated in 92 primary and 12 metastatic breast cancers by the use of immunohisto/cytochemistry with three monoclonal antibodies (MAbs) (JSB-1, C219, MRK16), and an RNAse protection assay. Follow-up information was available for 77 primary breast cancer patients (median follow-up 42 months; range 2-63 months). Results: Concordance among the anti-Pgp MAbs varied, the highest being between JSB-1 and MRK16 (71%; p = 0.002). Pgp expression was more frequent in metastatic disease (58%) than in primary breast cancer (29%) (JSB-1; p {box drawings light horizontal} 0.055). Pgp expression as assess th JSB-1 (univariateanalysis; p <0.05) was associated with shorter overall survival (OS). Nineteen (21%) primary breast cancers had Pgp expression in fibroblasts in desmoplastic stroma and this did not correlate with Pgp expression in the tumor. The combination of Pgp-positive tumor cells and Pgp-expressing fibroblasts was the strongest prognostic factor for OS by multi-variate analysis. Subgroup analysis suggested that Pgp expression was associated with a shorter OS in tamoxifen-treated patients, but not in those who received chemotherapy (most often CMF). Conclusions: Pgp expression in tumor cells, and especially when accompanied by Pgp expression in fibroblasts in desmoplastic stroma, has prognostic value in primary breast cancer patients and is likely to be a marker of a more malignant phenotype. Pgp expression of tumor cells might play a role in tamoxifen resistance. These findings may have important implications for the treatment of breast cancer patients, and warrant further prospective investigation in a larger patient population.

Original languageEnglish (US)
Pages (from-to)679-685
Number of pages7
JournalAnnals of Oncology
Volume6
Issue number7
StatePublished - Sep 1995
Externally publishedYes

Keywords

  • Breast cancer
  • Fibroblast
  • MDR1
  • Tamoxifen

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Neuropsychology and Physiological Psychology
  • Hematology
  • Oncology
  • Cancer Research

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