P-glycoprotein expression and multidrug resistance in adrenocortical carcinoma.
BACKGROUND
The response of adrenocortical carcinoma (ACC) to adjuvant chemotherapy has been disappointing with no significant impact on survival. The normal adrenal cortex has very high levels of P-glycoprotein, an energy-dependent efflux pump of a variety of structurally unrelated chemotherapeutic agents. P-glycoprotein has been implicated as a cause of multidrug resistance in a variety of neoplasms. The purpose of this study was to evaluate P-glycoprotein expression in ACC.


METHODS
Eleven patients with ACC had paraffin-embedded tumor evaluated for P-glycoprotein expression. These were analyzed by immunohistochemistry assay with a battery of four anti-P-glycoprotein antibodies (MRK-16, JSB-1, UIC-2, MDR).


RESULTS
All eleven cases showed intense, predominantly membrane immunoreactivity for P-glycoprotein. In 10 of the cases, most tumor cells were immunoreactive with at least three antibodies, and six of 11 cases were positive for all four antibodies. In this small series no correlation existed between P-glycoprotein expression and tumor grade, stage of disease, or survival.


CONCLUSIONS
All 11 cases of ACC studied showed P-glycoprotein expression, which was similar to the normal adrenal cortex. This possible mechanism of multidrug resistance may help explain the significant chemoresistance seen in ACC.
Flynn
S D
SD
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510.
Murren
J R
JR
Kirby
W M
WM
Honig
J
J
Kan
L
L
Kinder
B K
BK
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins