Expression of
P-glycoprotein, a phylogenetically conserved integral plasma membrane
protein, is implicated as one of the most important factors contributing to
tumor cell multidrug resistance.
Formalin-fixed,
paraffin-embedded normal and neoplastic canine tissues were studied using an
avidin-
biotin complex technique employing three murine
monoclonal antibodies (C494, C219, JSB-1) to different
epitopes of the
P-glycoprotein molecule. Evaluation of immunostaining of normal canine tissues revealed positive labeling detected by each antibody in the liver, proximal renal tubular epithelium, adrenal cortex, colonic epithelium, and capillary endothelial cells of the brain. A total of 166
tumors of epithelial or mesenchymal origin were evaluated for
P-glycoprotein immunoreactivity.
Hepatomas (4/4), colorectal
adenomas (7/7),
colorectal carcinomas (4/4),
adrenal cortical adenomas (3/3),
hemangiopericytomas (15/15), apocrine gland
adenocarcinomas (4/5, 80%), and
transitional cell carcinomas (2/2) consistently labeled with at least one of the
antibodies.
Histiocytomas (0/10), cutaneous
plasma cell tumors (0/10),
fibromas (0/3),
fibrosarcomas (0/4), and
leiomyomas (0/4) were uniformly negative with all
antibodies.
Malignant lymphomas (6/22, 27.3%),
malignant melanomas (4/13, 30.8%),
leiomyosarcomas (3/6, 50%), mammary gland
carcinomas (12/19, 63.2%), mammary gland
adenomas (3/9, 33.3%),
squamous cell carcinomas (8/10, 80%), basal cell
tumors (5/7, 71.4%), apocrine gland
adenomas (1/2, 50%),
cholangiocarcinomas (2/3, 66.7%), and thyroid gland
carcinomas (2/4, 50%) gave variable results. The
antibodies C494, JSB-1, and C219 labeled 66/166 (39.8%), 53/166 (31.9%), and 38/166 (22.9%) of all
tumors studied, respectively. A total of 26/166 (15.7%), 22/166 (13.3%), and 37/166 (22.6%) of
tumors were labeled by all three, just two, or one antibody alone, respectively. The antibody C494 was the only antibody labeling 28/166 (16.9%) of the cases. JSB-1 alone labeled 9/166 (5.4%) of the
tumors. C219 failed to label any
tumors not also labeled by either C494 or JSB-1. Labeling by C494 was more intense and specific than labeling by the other two
antibodies. Results indicate that
P-glycoprotein can be detected in routinely processed canine tissues. The detection of
P-glycoprotein within canine liver, kidney, adrenal gland, and colon and within
tumors arising from these tissues is consistent with that reported in the literature for human tissues. Variable labeling results of other
tumors such as
malignant lymphoma and mammary gland
carcinomas also is consistent with reports of human studies. Detection of multidrug resistance markers such as
P-glycoprotein in canine tissues may provide additional information upon which to base a prognosis or to design treatment regimens for canine
tumors.