title: Expression of multidrug resistance-related proteins p-glycoprotein, glutathione-s-transferases, topoisomerase-II and lung resistance protein in primary gastric cardiac adenocarcinoma.
abstract: OBJECTIVE
  Multidrug resistance (MDR) is closely correlated to an unfavorable prognosis in various human cancers. However, the clinical significance of the expression of MDR-related proteins p-glycoprotein (PGP), glutathione-s-transferases (GST-pi), topoisomerase-II (Topo-II) and lung resistance protein (LRP) in primary gastric cardiac adenocarcinoma (PGCA) remains unclear. In this study, the total of the four kinds of MDR-related proteins mentioned above were detected by using immunohistochemistry and their clinical significance in chemoresistance were also investigated.
  
  
  METHODS
  This retrospective study included 69 resected specimens from patients with PGCA. The expression of PGP, GST-pi, Topo-II and LRP in formalin-fixed paraffin-embedded tissue sections was determined by a labelled streptavidin-biotin immunohistochemical technique, and the results were analyzed in correlation with clinicopathological data. None of these patients received chemotherapy prior to surgery.
  
  
  RESULTS
  The positive rates of expression of PGP, GST-pi, Topo-II and LRP in malignant tissues (49.2%, 75.4%, 68.1% and 58%, respectively) were all higher than that of the normal tissues (0, 30%, 20% and 0, respectively, P<0.01). PGP expression in tumors that had metastasized was significantly more frequent than in tumors that had not metastasized (67.5% vs. 24.1%, P<0.01).The expression of PGP was closely related with clinicopathologic staging (staging 1/2 vs. 3/4, 28.6% vs. 58.3%, P<0.05). No significant correlation was shown between PGP and increasing differentiated degree (40%, 42.4% and 61.5%, P>0.05). GST-pi expression status progressively increased with increasing differentiated degree (40%, 75.8% and 88.5%, P<0.05) and clinico pathologic stage (staging 1/2 vs. 3/4, 57.1% vs. 83.3%, P<0.05). In addition, a significant positive correlation was also observed between GST-pi and lymphatic metastasis (with vs. without metastasis, 87.5% vs. 58.6%, P<0.05). The expression of Topo-II was associated with increasing differentiated degree (33.3%, 69.7% and 80.7%, P<0.01). No significant differences with Topo-II expression was found in relation to the clinicopathologic stage (staging 1/2 vs. 3/4, 57.1% vs. 72.9%, P>0.05) and lymphatic metastasis (with vs. without metastasis, 65.0% vs. 72.4%, P>0.05). Moreover, a significant difference with the expression of LRP was found in relation to the clinicopathologic stage (staging 1/2 vs. 3/4, 38% vs. 66.6%, P<0.05), and lymphatic metastasis (with vs. without metastasis, 70.0% vs. 41.4%, P<0.05). Comparing the well, moderately and poorly differentiated cohort, a non-statistical increasing trend towards LRP expression status was noted (50.0%, 54.5% and 65.3%, respectively, P>0.05). Besides, the co-expression of all four tested MDR-related proteins also existed. The positive rates of co-expression of PGP and GST-pi, PGP and Topo-II, PGP and LRP, GST-pi and Topo-II, LRP and GST-pi, LRP and Topo-II, PGP, GST-pi, Topo-II and LRP in malignant cells were 23.2%, 15.9%, 11.6%, 13.0%, 26.1%, 7.24%, 5.8%, respectively.
  
  
  CONCLUSIONS
  MDR-related proteins PGP, GST-pi, Topo-II and LRP are involved in multiple mechanisms of drug resistance in PGCA. Combined determination of PGP, GST-pi, Topo-II and LRP may be prospectively valuable for optimizing the chemotherapy regimes, developing high quality anti-cancer drugs, and further predicting the outcomes of those patients with PGCA.
authors.affiliation: Department of Cardiothoracic Surgery, Clinical College Yangzhou University, Yangzhou 225001, Jiangsu Province, China. shihongcan@gmail.com.cn
authors.forename: Hongcan
authors.initials: H
authors.lastname: Shi
authors.forename: Dan
authors.initials: D
authors.lastname: Lu
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Shu
authors.forename: Weiping
authors.initials: W
authors.lastname: Shi
authors.forename: Shichun
authors.initials: S
authors.lastname: Lu
authors.forename: Kang
authors.initials: K
authors.lastname: Wang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000230:Adenocarcinoma / Q000737:chemistry* / Q000188:drug therapy; D000328:Adult; D000368:Aged; D002299:Cardia / Q000737:chemistry*; D004250:DNA Topoisomerases, Type II / Q000032:analysis*; D019008:Drug Resistance, Neoplasm; D005260:Female; D051549:Glutathione S-Transferase pi / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000188:drug therapy; D020394:Vault Ribonucleoprotein Particles / Q000032:analysis*; D000099187:Major Vault Protein
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004250:DNA Topoisomerases, Type II; D051549:Glutathione S-Transferase pi; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein