title: Prognostic Value of Malic Enzyme and ATP-Citrate Lyase in Non-Small Cell Lung Cancer of the Young and the Elderly.
abstract: BACKGROUND
  Lung cancer is the leading cause of death among malignancies worldwide. Understanding its biology is therefore of pivotal importance to improve patient's prognosis. In contrast to non-neoplastic tissues, cancer cells utilize glucose mainly for production of basic cellular modules '(i.e. nucleotides, aminoacids, fatty acids). In cancer, Malic enzyme (ME) and ATP-citrate lyase (ACLY) are key enzymes linking aerobic glycolysis and fatty acid synthesis and may therefore be of biological and prognostic significance in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  ME and ACLY expression was analyzed in 258 NSCLC in correlation with clinico-pathological parameters including patient's survival.
  
  
  RESULTS
  Though, overall expression of both enzymes correlated positively, ACLY was associated with local tumor stage, whereas ME correlated with occurrence of mediastinal lymph node metastases. Young patients overexpressing ACLY and/or ME had a significantly longer overall survival. This proved to be an independent prognostic factor. This contrasts older NSCLC patients, in whom overexpression of ACLY and/or ME appears to predict the opposite.
  
  
  CONCLUSIONS
  In NSCLC, ME and ACLY show different enzyme expressions relating to local and mediastinal spread. Most important, we detected an inverse prognostic impact of ACLY and/or ME overexpression in young and elderly patients. It can therefore be expected, that treatment of NSCLC especially, if targeting metabolic pathways, requires different strategies in different age groups.
authors.affiliation: Department of Pathology, Institute of Surgical Pathology, University Medical Center Freiburg, Breisacher Strasse 115a, D-79106 Freiburg, Germany.
authors.forename: Agnes
authors.initials: A
authors.lastname: Csanadi
authors.affiliation: Department of Pathology, Institute of Surgical Pathology, University Medical Center Freiburg, Breisacher Strasse 115a, D-79106 Freiburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kayser
authors.affiliation: Department of Pathology, Institute of Surgical Pathology, University Medical Center Freiburg, Breisacher Strasse 115a, D-79106 Freiburg, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Donauer
authors.affiliation: Clinical Cancer Registry, Comprehensive Cancer Center Freiburg, University Medical Center Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Gumpp
authors.affiliation: Department of Pathology, Institute of Surgical Pathology, University Medical Center Freiburg, Breisacher Strasse 115a, D-79106 Freiburg, Germany.
authors.forename: Konrad
authors.initials: K
authors.lastname: Aumann
authors.affiliation: Department of Hematology and Oncology, University Medical Center Freiburg, Hugstetter Strassse 55, D-79106 Freiburg, Germany.
authors.forename: Justyna
authors.initials: J
authors.lastname: Rawluk
authors.affiliation: Department of Pneumonology, Hannover Medical School, Carl-Neuberg Strasse 1, D-30625 Hannover, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Prasse
authors.affiliation: Department of Pathology, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Axel
authors.initials: A
authors.lastname: zur Hausen
authors.affiliation: Department of Thoracic Surgery, University Medical Center Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wiesemann
authors.affiliation: Department of Pathology, Institute of Surgical Pathology, University Medical Center Freiburg, Breisacher Strasse 115a, D-79106 Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
authors.affiliation: Department of Pathology, Institute of Surgical Pathology, University Medical Center Freiburg, Breisacher Strasse 115a, D-79106 Freiburg, Germany.
authors.forename: Gian
authors.initials: G
authors.lastname: Kayser
mesh_terms: D001275:ATP Citrate (pro-S)-Lyase / Q000378:metabolism*; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008291:Malate Dehydrogenase / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis
chemical_list: D008291:Malate Dehydrogenase; D001275:ATP Citrate (pro-S)-Lyase