Immunohistochemical study of permeability glycoprotein expression in canine perianal tumors https://doi.org/10.12982/VIS.2025.071
Main Article Content
Abstract
Perianal gland tumors are androgenic hormone-dependent and commonly found in dogs. Permeability glycoprotein (PGP) is a member of the ATP-binding cassette transporter family, playing an essential role in reducing intracellular drug concentration and limiting drug cytotoxicity in cancer cells, leading to multi-drug resistance. This study aims to investigate PGP expression patterns in perianal gland tumors. Sixty-four specimens from 64 dogs were histologically classified as perianal gland adenoma (59.38%), perianal gland epithelioma (12.50%), and perianal carcinoma (28.13%). All samples are analyzed for PGP expression using immunohistochemistry, scoring for percentage positivity and intensity. Four cases (6.25%) have a positive expression of PGP with intense cytoplasmic staining. There was a significant difference in the PGP expression pattern among the groups (p=0.01). The expression of PGP may provide valuable insights into disease prognosis and prediction of clinical outcomes of chemotherapy treatment in dogs with perianal gland tumors
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publishing an article with open access in Veterinary Integrative Sciences leaves the copyright with the author. The article is published under the Creative Commons Attribution License 4.0 (CC-BY 4.0), which allows users to read, copy, distribute and make derivative works from the material, as long as the author of the original work is cited.
References
Alfarouk, K.O., Stock, C.M., Taylor, S., Walsh, M., Muddathir, A.K., Verduzco, D., Bashir, A.H., Mohammed, O.Y., Elhassan, G.O., Harguindey, S., 2015. Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp. Cancer. Cell. Int. 15, 1-13.
Ardelli, B.F., Prichard, R.K., 2013. Inhibition of P-glycoprotein enhances sensitivity of Caenorhabditis elegans to ivermectin. Vet. Parasitol. 191, 264-275.
Baekelandt, M.M., Holm, R., Nesland, J.M., Tropé, C.G., Kristensen, G.B., 2000. P-glycoprotein expression is a marker for chemotherapy resistance and prognosis in advanced ovarian cancer. Anticancer. Res. 20, 1061-1067.
Berrocal, A., Vos, J., Van Den Ingh, T., Molenbeek, R., Van Sluijs, F., 1989. Canine perineal tumours. J. Vet. Med. Ser. A. 36, 739-749.
Bosch, I., Croop, J., 1996. P-glycoprotein multidrug resistance and cancer. Biochim. Biophys. Acta. Reviews on Cancer. 1288, F37-F54.
Brodzki, A., Łopuszyński, W., Brodzki, P., Głodkowska, K., Knap, B., Gawin, P., 2023. Pharmacological Treatment of Perianal Gland Tumors in Male Dogs. Animals. 13, 463.
Chang, S.C., Chen, Y.K., Cheng, Y.C., Chen, Y.C., Liao, J.W., 2017. Tumor-Infiltrating Lymphocytes and P-Glycoprotein/Melanoma Antigen a Expression in Vincristine-Treated Canine Transmissible Venereal Tumors. Taiwan. Vet. J. 43, 285-293.
de Lange, E.C., 2004. Potential role of ABC transporters as a detoxification system at the blood–CSF barrier. Adv. Drug Deliv. Rev. 56, 1793-1809.
Demeule, M., Labelle, M., Régina, A., Berthelet, F., Béliveau, R., 2001. Isolation of endothelial cells from brain, lung, and kidney: expression of the multidrug resistance P-glycoprotein isoforms. Biochem. Biophys. Res. Commun. 281, 827-834.
Fromm, M.F., 2004. Importance of P-glycoprotein at blood–tissue barriers. Trends. Pharmacol. Sci. 25, 423-429.
Ginn, P., 1996. Immunohistochemical detection of P-glycoprotein in formalin-fixed and paraffin-embedded normal and neoplastic canine tissues. Vet. Pathol. 33, 533-541.
Ieiri, I., 2012. Functional significance of genetic polymorphisms in P-glycoprotein (MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2). Drug. Metab. Pharmacokinet. 27, 85-105.
Jakab, C., Rusvai, M., Szabo, Z., Szabara, A., Kulka, J., 2009. Expression of the claudin-4 molecule in benign and malignant canine hepatoid gland tumours. Acta. Vet. Hung. 57, 463-475.
Kim, J.W., Park, Y., Roh, J.-L., Cho, K.-J., Choi, S.-H., Nam, S.Y., Kim, S.Y., 2016. Prognostic value of glucosylceramide synthase and P-glycoprotein expression in oral cavity cancer. Int. J. Clin. Oncol. 21, 883-889.
Kim, S.H., Seung, B.J., Cho, S.H., Lim, H.Y., Hwang, J.H., Sur, J.H., 2018. Expression of oestrogen receptor, progesterone receptor and akt in canine circumanal gland tumours. J. Comp. Pathol. 162, 59-65.
Lee, G., Bendayan, R., 2004. Functional expression and localization of P-glycoprotein in the central nervous system: relevance to the pathogenesis and treatment of neurological disorders. Pharm. Res. 21, 1313-1330.
Levi, M., Brunetti, B., Sarli, G., Benazzi, C., 2016. Immunohistochemical Expression of P-glycoprotein and breast cancer resistance protein in canine mammary hyperplasia, neoplasia and supporting stroma. J. Comp. Pathol. 155, 277-285.
Levi, M., Pena, L., Alonso-Diez, A., Brunetti, B., Muscatello, L.V., Benazzi, C., Perez-Alenza, M.D., Sarli, G., 2019. P-Glycoprotein and breast cancer resistance protein in canine inflammatory and noninflammatory grade III mammary carcinomas. Vet. Pathol. 56, 840-847.
Linn, S., Giaccone, G., 1995. MDR1/P-glycoprotein expression in colorectal cancer. Eur. J. Cancer. 31, 1291-1294.
Martins, A.L., Canadas-Sousa, A., Mesquita, J.R., Dias-Pereira, P., Amorim, I., Gärtner, F., 2022. Retrospective study of canine cutaneous tumors submitted to a diagnostic pathology laboratory in Northern Portugal (2014–2020). Canine. Med. Genet. 9, 2.
McCourt, M.R., Levine, G.M., Breshears, M.A., Wall, C.R., Meinkoth, J.H., 2018. Metastatic disease in a dog with a well‐differentiated perianal gland tumor. Vet. Clin. Pathol. 47, 649-653.
Nanayakkara, A.K., Follit, C.A., Chen, G., Williams, N.S., Vogel, P.D., Wise, J.G., 2018. Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality of multidrug resistant tumor cells. Sci. Rep. 8, 967.
Pereira, R.S., Schweigert, A., Melo, G.D.d., Fernandes, F.V., Sueiro, F.A.R., Machado, G.F., 2013. Ki-67 labeling in canine perianal glands neoplasms: a novel approach for immunohistological diagnostic and prognostic. BMC Vet. Res. 9, 1-7.
Petterino, C., Martini, M., Castagnaro, M., 2004. Immunohistochemical detection of growth hormone (GH) in canine hepatoid gland tumors. J. Vet. Med. Sci. 66, 569-572.
Saeed, M., Zeino, M., Kadioglu, O., Volm, M., Efferth, T., 2014. Overcoming of P-glycoprotein-mediated multidrug resistance of tumors in vivo by drug combinations. Synergy. 1, 44-58.
Schneider, J., Bak, M., Efferth, T., Kaufmann, M., Mattern, J., Volm, M., 1989. P-glycoprotein expression in treated and untreated human breast cancer. Br. J. Cancer. 60, 815-818.
Sharom, F.J., 2011. The P-glycoprotein multidrug transporter. Essays. Biochem. 50, 161-178.
Simeonov, R., 2019. Nuclear morphometry in 36 canine spontaneous perianal gland tumours. Vet. Ital. 55, 307-310.
Stępień, K.M., Tomaszewski, M., Tomaszewska, J., Czuczwar, S.J., 2012. The multidrug transporter P-glycoprotein in pharmacoresistance to antiepileptic drugs. Pharmacol. Rep. 64, 1011-1019.
Stern, A.W., Young, A.J., Pieper, J.B., 2018. Cytokeratin Profiles Of Canine Anal Sac And Hepatoid Gland Neoplasms. Taiwan. Vet. J. 44, 119-123.
Szakács, G., Paterson, J.K., Ludwig, J.A., Booth-Genthe, C., Gottesman, M.M., 2006. Targeting multidrug resistance in cancer. Nat. Rev. Drug Discov. 5, 219-234.
Thomas, R., Fox, L., 1998. Tumors of the skin and subcutis, Perianal (hepatoid) gland tumors. Cancer in Dogs and Cats. Williams & Wilkins, Baltimore, pp. 497-498.
Tozon, N., Kodre, V., Juntes, P., Sersa, G., Cemazar, M., 2010. Electrochemotherapy is highly effective for the treatment of canine perianal hepatoid adenoma and epithelioma. Acta. Vet. 60, 285-302.
Tozon, N., Kodre, V., Sersa, G., Cemazar, M., 2005. Effective treatment of perianal tumors in dogs with electrochemotherapy. Anticancer. Res. 25, 839-845.
Vail, D., Withrow, S., Schwarz, P., Powers, B., 1990. Perianal adenocarcinoma in the canine male: a retrospective study of 41 cases. J. Am. Anim. Hosp. Assoc. 26, 329-334.
Van der Heyden, S., Chiers, K., Vercauteren, G., Daminet, S., Wegge, B., Paepe, D., Ducatelle, R., 2011a. Expression of multidrug resistance-associated P-glycoprotein in feline tumours. J. Comp. Pathol. 144, 164-169.
Van der Heyden, S., Vercauteren, G., Daminet, S., Paepe, D., Chiers, K., Polis, I., Waelbers, T., Hesta, M., Schauvliege, S., Wegge, B., Ducatelle, R., 2011b. Expression of P-glycoprotein in the intestinal epithelium of dogs with lymphoplasmacytic enteritis. J. Comp. Pathol. 145, 199-206.
Waghray, D., Zhang, Q., 2017. Inhibit or evade multidrug resistance P-glycoprotein in cancer treatment: Miniperspective. J. Med. Chem. 61, 5108-5121.
Weinstein, R., Grogan, T., Kuszak, J., Jakate, S., Kluskens, L., Coon, J., 1991. Multidrug resistance gene product (P-glycoprotein) in normal tissue and tumors. Adv. Pathol. Labor. Med. 10, 207-234.
Wilson, G., Hayes Jr, H., 1979. Castration for treatment of perianal gland neoplasms in the dog. J. Am. Vet. Med. Assoc. 174, 1301-1303.
Withrow, S.J., Vail, D.M., Page, R.L., 2013. Withrow and MacEwen's small animal clinical oncology. Available online: https://doi.org/10.1016/C2009-0-53135-2.
Zandvliet, M., Teske, E., Schrickx, J.A., 2014. Multi-drug resistance in a canine lymphoid cell line due to increased P-glycoprotein expression, a potential model for drug-resistant canine lymphoma. Toxicol. In Vitro. 28, 1498-1506.