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P-glycoprotein expression and multidrug resistance in adrenocortical carcinoma

S D Flynn1, J R Murren, W M Kirby

  • 1Department of Pathology, Yale University School of Medicine, New Haven, CT 06510.

Surgery
|December 1, 1992
PubMed
Abstract

Insights

Adrenocortical carcinoma (ACC) exhibits significant chemoresistance due to high P-glycoprotein expression. This multidrug resistance protein, found in all studied ACC cases, may explain poor treatment response and limited survival impact from chemotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Adrenocortical carcinoma (ACC) shows poor response to adjuvant chemotherapy, impacting patient survival.
  • The normal adrenal cortex expresses high levels of P-glycoprotein, a key factor in multidrug resistance.
  • P-glycoprotein is implicated in multidrug resistance across various neoplasms.

Purpose of the Study:

  • To investigate P-glycoprotein expression in adrenocortical carcinoma (ACC).
  • To determine if P-glycoprotein contributes to chemoresistance in ACC.

Main Methods:

  • Paraffin-embedded tumor samples from eleven ACC patients were analyzed.
  • Immunohistochemistry assays using four distinct anti-P-glycoprotein antibodies (MRK-16, JSB-1, UIC-2, MDR) were employed.

Main Results:

  • All eleven ACC cases demonstrated intense P-glycoprotein immunoreactivity, primarily at the cell membrane.
  • Ten cases showed reactivity with at least three antibodies; six cases were positive for all four.
  • No correlation was found between P-glycoprotein expression and tumor grade, stage, or survival in this cohort.

Conclusions:

  • P-glycoprotein is consistently expressed in adrenocortical carcinoma (ACC) at levels comparable to the normal adrenal cortex.
  • Elevated P-glycoprotein expression presents a potential mechanism for the observed multidrug resistance and chemoresistance in ACC.

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