title: Tumor type M2-pyruvate-kinase levels in pleural fluid versus plasma in cancer patients: a further tool to define the need for invasive procedures.
abstract: OBJECTIVE
  Pleural effusion is a common diagnostic problem and a challenge to the thoracic surgeon. The analysis of serum and body fluids for tumor markers is an established diagnostic procedure. Among various markers, tumors are linked to the overexpression of a glycolytic isoenzyme, M2-pyruvate-kinase (M2-PK). This preliminary study evaluated this enzyme as a tumor marker to differentiate malignant from benign pleural effusion.
  
  
  METHODS
  The tumor M2-PK concentration was measured in the EDTA-plasma and pleural fluid of 34 patients with an established diagnosis of cancer, either primary of the chest (18) or secondary to chest (16) and in 34 controls with benign effusion. The concentration was quantitatively determined by an enzyme-linked immunosorbent assay. The cut-off level between negative and positive values of the tumor M2-PK was defined as the benign group's mean+2SD (95% percentile). True-positives, false-positives, true-negatives, and false-negatives, were determined with 'positive' referring to histologically proven malignant effusion and 'negative' referred to as nonmalignant effusions. Sensitivity, specificity, positive predictive value, and negative predictive value were assessed.
  
  
  RESULTS
  The cut-off value was established at 7.61 U/ml for plasma and 32.9 U/ml for pleural fluid. Both plasma and pleural fluid levels of tumor M2-PK were significantly higher in patients with known chest malignancy, either primary or metastatic, compared to nonmalignant effusions (p<0.001). Sensitivity in pleural fluid was significantly higher compared to plasma (85.7% vs 76.2%; p<0.01). Moreover, negative predictive value was higher for pleural fluid compared to plasma (79.4% vs 70.8; p<0.01)
  
  
  CONCLUSIONS
  Tumor M2-PK marker is useful in differentiating malignant from benign pleural effusions. Moreover, its sensitivity and NPV in pleural fluid are significantly higher compared to plasma. The usefulness of such a test is not strictly diagnostic but aims at excluding poorly performing patients from further invasive procedures. Thus, the inclusion of M2-PK within a panel of well-known tumor markers such as CEA, MCA, Ca 125 and Ca 19-9, may help in increasing the overall sensitivity and specificity.
authors.affiliation: Department of Thoracic Surgery, Tor Vergata University, Viale Oxford 81, I-00133 Rome, Italy. elia@med.uniroma.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Elia
authors.forename: Renato
authors.initials: R
authors.lastname: Massoud
authors.forename: Gianluca
authors.initials: G
authors.lastname: Guggino
authors.forename: Benedetto
authors.initials: B
authors.lastname: Cristino
authors.forename: Claudio
authors.initials: C
authors.lastname: Cortese
authors.forename: Alessia Raffaella
authors.initials: AR
authors.lastname: De Massimi
authors.forename: Rossella
authors.initials: R
authors.lastname: Zenobi
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D001826:Body Fluids / Q000201:enzymology*; D004796:Clinical Enzyme Tests; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016066:Pleural Effusion, Malignant / Q000175:diagnosis* / Q000473:pathology; D011770:Pyruvate Kinase / Q000097:blood / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013899:Thoracic Neoplasms / Q000175:diagnosis* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D011770:Pyruvate Kinase