title: Correlation between expression of metallothionein and expression of Ki-67 and MCM-2 proliferation markers in non-small cell lung cancer.
abstract: BACKGROUND
  Metallothioneins (MTs) are low molecular weight proteins present both in normal and neoplastic cells. They protect cells from the effects of heavy metals and from damage induced by free radicals. MT bind heavy metals, exert an anti-apoptotic effect and stimulate proliferation of neoplastic cells. The role of MTs in carcinogenesis has not been fully clarified yet. This study aimed at the evaluation of the intensity of metallothionein (MT-I/II) expression in various histological types of non-small cell lung cancer (NSCLC) and correlation of the expression intensity with clinical/pathological parameters and Ki-67 and minichromosome maintaince protein 2 (MCM-2) proliferation markers.
  
  
  METHODS
  The studies were performed on archival material, originating from 145 patients, 105 men and 40 women (65 adenocarcinomas, 67 squamous cell carcinomas, 13 large cell carcinomas).
  
  
  RESULTS
  A positive correlation was noted between expression of MT-I/II and expressions of Ki-67 (r=0.1863, p=0.0248) and MCM-2 (r=0.1766, p=0.0336) in NSCLC overall. The most pronounced expression of MT-I/II was noted in the large cell carcinomas. The expression of MT-I/II was significantly lower in the adenocarcinomas than in the squamous cell carcinomas (p=0.0028) and large cell carcinomas (p=0.0485). The expression of MT-I/II showed no differences related to individual degrees of NSCLC malignancy. Univariate analysis demonstrated no significant differences in overall survival related to the expression intensity of MT-I/II, Ki-67 or MCM-2, but the survival of the patients with high expression of MT-I/II and Ki-67 in the neoplastic cells, as compared to low expression of MT-I/II and Ki-67, was shorter (the difference approached statistical significance, p=0.067).
  
  
  CONCLUSIONS
  MT-I/II expression is evident in proliferating NSCLC neoplastic cells, pointing to the prognostic importance of parallel expression of MT-I/II and Ki-67.
authors.affiliation: Department of Pulmonology and Pulmonary Tumours, Medical University in Wroclaw, Wroclaw, Poland.
authors.forename: Bozena
authors.initials: B
authors.lastname: Werynska
authors.forename: Bartosz
authors.initials: B
authors.lastname: Pula
authors.forename: Beata
authors.initials: B
authors.lastname: Muszczynska-Bernhard
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Piotrowska
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jethon
authors.forename: Marzena
authors.initials: M
authors.lastname: Podhorska-Okolow
authors.forename: Piotr
authors.initials: P
authors.lastname: Dziegiel
authors.forename: Renata
authors.initials: R
authors.lastname: Jankowska
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D008668:Metallothionein; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2