title: Concomitance of P-gp/LRP Expression with EGFR Mutations in Exons 19 and 21 in Non-Small Cell Lung Cancers.
abstract: OBJECTIVE
  Traditional chemotherapy is the main adjuvant therapy for the treatment of non-small cell lung cancer (NSCLC). However, the emergence of multi-drug resistance (MDR) has greatly restricted the curative effect of chemotherapy. Therefore, it is necessary to find a method to treat MDR NSCLC clinically. It is worth investigating whether NSCLCs that are resistant to traditional chemotherapy can be effectively treated with tyrosine kinase inhibitors targeting epidermal growth factor receptor (EGFR).
  
  
  METHODS
  The expression of P-glycoprotein (P-gp) and lung resistance-related protein (LRP) was detected by immunohistochemistry, and mutations in EGFR (exons 19 and 21) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (exon 2) were detected by high-resolution melting analysis (HRMA) of surgical NSCLC specimens from 127 patients who did not undergo traditional chemotherapy or radiotherapy. A Pearson chi-square test was performed to analyze the correlations between the expression of P-gp and LRP and mutations in EGFR and KRAS.
  
  
  RESULTS
  The expression frequencies of P-gp and LRP were significantly higher in adenocarcinomas from non-smoking patients; the expression frequency of LRP was significantly higher in cancer tissue from female patients. The frequency of EGFR mutations was significantly higher in well to moderately differentiated adenocarcinomas from non-smoking female patients. The frequency of EGFR mutations in the cancers that expressed P-gp, LRP, or both P-gp and LRP was significantly higher than that in cancers that did not express P-gp or LRP.
  
  
  CONCLUSIONS
  NSCLCs expressing P-gp/LRP bear the EGFR mutation in exon 19 or 21 easily.
authors.affiliation: MD Candidate in Pathology, Dalian Medical University, Dalian, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.affiliation: MD Candidate in Pathology, Dalian Medical University, Dalian, China.
authors.forename: Weipeng
authors.initials: W
authors.lastname: Lu
authors.affiliation: Central Laboratory, The Second Hospital of Dalian Medical University, Dalian, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathology, The First Hospital of Dalian Medical University, Dalian, China.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Central Laboratory, The Second Hospital of Dalian Medical University, Dalian, China. lvshen1956@126.com.
authors.forename: Shen
authors.initials: S
authors.lastname: Lu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000601:surgery; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics*; D000099187:Major Vault Protein
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D066246:ErbB Receptors; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D020394:Vault Ribonucleoprotein Particles; D018631:ras Proteins; D000099187:Major Vault Protein; C117307:KRAS protein, human; C512478:EGFR protein, human
keywords: Chemotherapy; epidermal growth factor receptor-tyrosine kinase inhibitor; multi-drug resistance; non-small cell lung cancer