title: Pyruvate kinase isoenzyme M2 is not of diagnostic relevance as a marker for oral cancer.
abstract: BACKGROUND
  Increased aerobic glycolysis is one of the most common abnormalities occurring in the metabolism of tumour cells with pyruvate kinase as one of the key glycolytic enzymes. The dimeric form of M2-pyruvate kinase, found predominantly in tumour cells, is designated as tumour M2-pyruvate kinase (TuM2-PK). The aim of the present, prospective study was to evaluate the diagnostic relevance of TuM2-PK in detecting oral squamous cell carcinoma (OSCC).
  
  
  METHODS
  TuM2-PK concentration was analysed in ethylene diaminetetraacetic acid plasma of 80 untreated patients with histologically confirmed OSCC stages T3 and T4, whilst 90 patients with non-malignant diseases served as controls. The analysis was done using a sandwich enzyme-linked immunosorbent assay (ScheBo Biotech AG, Giessen, Germany). Immunohistochemical detection of TuM2-PK was performed by specific mouse monoclonal antibody DF-4.
  
  
  RESULTS
  The median TuM2-PK concentration was 22.92U/ml in the tumour group and 10.00U/ml in the control group (p<0.001). Using 15U/ml as a cut-off yielded a sensitivity of 63% and a specificity of 59%. Moreover, the positive and negative predictive values were 57% and 64%, respectively. Immunohistochemical staining of tissue sections showed that TuM2-PK was not selectively expressed in tumour cells but also in non-malignant cells, particularly in more regenerative ones.
  
  
  CONCLUSIONS
  Low sensitivity and specificity for stages T3 and T4 OSCC render the TuM2-PK test unsuitable as a tool for detecting OSCC, particularly in an early stage. Thus, routine clinical and radiological follow-up is indispensable after treatment of OSCC.
authors.affiliation: Department of Maxillofacial & Facial Plastic Surgery, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. juergen.ervens@charite.de
authors.forename: Juergen
authors.initials: J
authors.lastname: Ervens
authors.forename: Hendrik
authors.initials: H
authors.lastname: Fuchs
authors.forename: Volker-Till
authors.initials: VT
authors.lastname: Niemann
authors.forename: Bodo
authors.initials: B
authors.lastname: Hoffmeister
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D016022:Case-Control Studies; D004796:Clinical Enzyme Tests; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006019:Glycolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000473:pathology; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011770:Pyruvate Kinase / Q000097:blood*; D018709:Statistics, Nonparametric
chemical_list: D014408:Biomarkers, Tumor; D011770:Pyruvate Kinase