Immunohistochemical Assessment of the Expression of Biliary Transportation Proteins MRP2 and MRP3 in Hepatocellular Carcinoma and in Cholangiocarcinoma

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Citações na Scopus
12
Tipo de produção
article
Data de publicação
2019
Título da Revista
ISSN da Revista
Título do Volume
Editora
SPRINGER
Citação
PATHOLOGY & ONCOLOGY RESEARCH, v.25, n.4, p.1363-1371, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Multidrug resistance-associated protein 2 (MRP2) is a multi-specific organic anion transporter predominantly expressed in the canalicular membrane of hepatocytes, epithelial cells from gallbladder and apical membranes of proximal tubular kidney epithelium whereas multidrug resistance-associated protein 3 (MRP3) is present in the basolateral membrane of hepatocytes and cholangiocytes. This study aims to detect the expression of these transporters in hepatocellular carcinoma (HCC) and in cholangiocarcinoma (CC), searching for evidences for future studies on differential diagnosis and on clinical essays. The immunohistochemical reactivity (IHC) of these transporters was assessed in tissue microarrays of 80 HCC and 56 CC cases using monoclonal antibodies and compared with anatomopathological (AP) variables. The positivity of MRP2 was observed in 92.3% of HCC and in 96.3% of CC. The detection of high MRP2 expression in HCC was not significantly different (p > 0.05) according to the size, number of nodules architectural pattern and growth pattern of HCC and CC. Regarding histological grades, 22/22 well moderately differentiated HCC versus 50/56 poorly differentiated HCC were positive for MRP2. A trend for lower expression in poor differentiation HCC was found. And 50/50 well/moderately differentiated CC versus 2/4 poorly/undifferentiated CC were positive for MRP2. This result showed a reduced expression (p = 0,0004) in poorly differentiated CC. MRP3 positivity was observed in 18.8% of HCC and was not significantly different according to AP parameters. MRP3 was expressed in 44.5% CC, with a trend for lower expression in less differentiated CC and significantly lower rates in the ductular histological subtype (p = 0.023). The high expression of MRP2 in HCC and in CC is conserved regardless most of the anatomopathological parameters, except for a trend of lower expression in less differentiated HCC and CC. The observation of lower MRP3 expression in less differentiated CC and, especially, in the histological subtype with expression of hepatic progenitor cell phenotypes leads to future opportunities to evaluate the expression of this marker in cholangiocarcinomas.
Palavras-chave
ATP-binding cassette transporters, Hepatocellular carcinoma, Cholangiocarcinoma, Immunohistochemistry
Referências
  1. Alrefai WA, 2007, PHARM RES, V24, P1803, DOI 10.1007/s11095-007-9289-1
  2. [Anonymous], 2017, ABCC3 ATP BIND CASS
  3. [Anonymous], 2017, ABCC3 ATP BIND CASS
  4. [Anonymous], ABCC2 ATP BIND CASS
  5. Apte U, 2011, MOL PATHOL LIB, V5, P147, DOI 10.1007/978-1-4419-7107-4_11
  6. Atilano-Roque A, 2016, J CLIN PHARMACOL, V56, pS205, DOI 10.1002/jcph.768
  7. Ballatori N, 2005, TOXICOL APPL PHARM, V204, P238, DOI 10.1016/j.taap.2004.09.008
  8. Belinsky MG, 2005, MOL PHARMACOL, V68, P160, DOI 10.1124/mol.104.010587
  9. Buettner S, 2017, ONCOTARGETS THER, V10, P1131, DOI 10.2147/OTT.S93629
  10. Chen ZL, 2016, CANCER LETT, V370, P153, DOI 10.1016/j.canlet.2015.10.010
  11. Erlinger S, 2014, GASTROENTEROLOGY, V146, P1625, DOI 10.1053/j.gastro.2014.03.047
  12. Fujikura K, 2016, AM J SURG PATHOL, V40, P689, DOI 10.1097/PAS.0000000000000585
  13. Halilbasic E, 2013, J HEPATOL, V58, P155, DOI 10.1016/j.jhep.2012.08.002
  14. Jedlitschky G, 2006, EXPERT OPIN DRUG MET, V2, P351, DOI 10.1517/17425255.2.3.351
  15. Keppler D, 2014, DRUG METAB DISPOS, V42, P561, DOI 10.1124/dmd.113.055772
  16. Klaassen CD, 2010, PHARMACOL REV, V62, P1, DOI 10.1124/pr.109.002014
  17. Konig J, 1999, HEPATOLOGY, V29, P1156, DOI 10.1002/hep.510290404
  18. Kool M, 1999, P NATL ACAD SCI USA, V96, P6914, DOI 10.1073/pnas.96.12.6914
  19. Korita PV, 2010, ONCOL REP, V23, P965, DOI 10.3892/or_00000721
  20. Lagana SM, 2015, HISTOPATHOLOGY, V66, P598, DOI 10.1111/his.12601
  21. Nakanuma Y, 2015, BEST PRACT RES CL GA, V29, P277, DOI 10.1016/j.bpg.2015.02.006
  22. Nies AT, 2002, EUR J BIOCHEM, V269, P1866, DOI 10.1046/j.1432-1033.2002.02832.x
  23. Nies AT, 2001, INT J CANCER, V94, P492, DOI 10.1002/ijc.1498
  24. Rau S, 2008, EUR J CLIN INVEST, V38, P134, DOI 10.1111/j.1365-2362.2007.01916.x
  25. Scheffer GL, 2000, CANCER RES, V60, P5269
  26. Sodani K, 2012, CHIN J CANCER, V31, P58, DOI 10.5732/cjc.011.10329
  27. Stefkova J, 2004, PHYSIOL RES, V53, P235
  28. Taniguchi K, 1996, CANCER RES, V56, P4124
  29. Tarling EJ, 2013, TRENDS ENDOCRIN MET, V24, P342, DOI 10.1016/j.tem.2013.01.006
  30. Nguyen T, 2015, ARCH PATHOL LAB MED, V139, P1028, DOI 10.5858/arpa.2014-0479-OA
  31. Tomonari T, 2016, ONCOTARGET, V7, P7207, DOI 10.18632/oncotarget.6889
  32. Trauner M, 2003, PHYSIOL REV, V83, P633, DOI 10.1152/physrev.00027.2002
  33. Vander Borght S, 2005, J PATHOL, V207, P471, DOI 10.1002/path.1852
  34. Vasiliou Vasilis, 2009, Human Genomics, V3, P281
  35. Zollner G, 2005, LIVER INT, V25, P367, DOI 10.1111/j.1478-3231.2005.01033.x