title: Integrin-Linked Kinase, Snail and Multidrug Resistance Protein 1: Three concordant players in the progression of non-small cell lung cancer.
abstract: BACKGROUND
  Integrin Linked Kinase (ILK), Snail and Multidrug Resistance Protein 1 (MRP1) have been implicated in several cancers; however, their roles in non-small cell lung cancer (NSCLC) remain to be elucidated.
  
  
  OBJECTIVE
  Investigation of their expression in NSCLC tissue. Relationships among these proteins and their association with clinicopathological parameters were studied.
  
  
  METHODS
  ILK, Snail and MRP1 expression were immunohistochemically assessed in 97 tumor tissues. Furthermore, western blot analysis for ILK, Snail and MRP1 in 6 cases of NSCLC was also performed.
  
  
  RESULTS
  ILK overexpression, positive Snail and MRP1 expression were found in 46.4%, 36.1% and 49.5% of tumors respectively. ILK expression was significantly correlated with tumor grade (p=0.013), lymph node (LN) metastases (p=0.001) and stage (p=0.001). Positive Snail and MRP1 expression were significantly associated with LN metastasis (p=0.004 and 0.022, respectively) and advanced stage disease (p=0.018 and 0.024, respectively). MRP1 expression was significantly higher among adenocarcinoma cases compared to other types (p=0.001). ILK over-expression was significantly associated with up-regulation of Snail and MRP1 (p<0.001 both). Significant association was also, found between Snail and MRP1 expression (p=0.005). Moreover, the co-expression of two markers or more was significantly associated with less differentiation (p=0.011), advanced tumor status (p=0.030), LN metastasis (p<0.001) and advanced stage (p<0.001) disease. Western blot analysis validated immunohistochemical findings.
  
  
  CONCLUSIONS
  ILK may have an important role in the progression of NSCLC, possibly through up-regulation of Snail and MRP1. ILK, Snail and MRP1 are important molecular markers for predicting carcinogenesis and progression of NSCLC.
authors.affiliation: Department of Pathology, Faculty of Medicine, Minia University, El-Minia, Egypt. Electronic address: dalia_abdelrehim@hotmail.com.
authors.forename: Dalia M
authors.initials: DM
authors.lastname: Abd El-Rehim
authors.affiliation: Department of Pathology, Faculty of Medicine, Minia University, El-Minia, Egypt.
authors.forename: Manal I
authors.initials: MI
authors.lastname: Abd-Elghany
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Minia University, El-Minia, Egypt.
authors.forename: Maiiada H
authors.initials: MH
authors.lastname: Nazmy
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D000099200:Scaffold Protein ILK
chemical_list: D014408:Biomarkers, Tumor; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017346:Protein Serine-Threonine Kinases; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D000099200:Scaffold Protein ILK; C421109:multidrug resistance-associated protein 1
keywords: ILK; Immunohistochemistry; MRP1; NSCLC; Snail; Western blot