title: Ploidy and Tn-antigen expression in the detection of transitional cell neoplasia in non-tumour-bearing patients.
abstract: OBJECTIVE
  To study the effectiveness of combining DNA ploidy and the blood-group related membrane antigen Tn as bladder tumour markers which have been individually associated with high tumour grade and poor prognosis. In particular to (i) determine whether use of these two markers would improve tumour detection compared with either alone, particularly of high grade disease and (ii) determine whether intermediate rates of marker expression would occur in bladder cancer patients with no current tumour compared with those with a tumour and a control group with benign prostatic hypertrophy.
  
  
  METHODS
  A total of 102 patients undergoing cystoscopic monitoring for either benign prostatic hyperplasia (BPH) or for transitional cell carcinoma (TCC) at the Repatriation Hospital and Flinders Medical Centre were included in the study. The patients comprised three study groups, those with BPH (n = 37), with TCC but no tumour present (n = 38) and those with TCC and a tumour present at cystoscopy (n = 27). Exfoliated cells obtained from bladder washings at cystoscopy were double-labelled using a monoclonal antibody to the Tn antigen and a DNA stain, propidium iodide and examined by flow cytometry.
  
  
  RESULTS
  Rates of marker expression in 27 patients with tumours were 30% for Tn antigen, 30% for aneuploidy and 48% for either marker. Marker expression was strongly associated with tumour grade, with no expression at grade 1, 38% (3/8) tumours at grade 2 and 90% (9/10) at grade 3. In patients with a history of bladder tumours but no current tumour, rates were intermediate (30%) compared with patients with current transitional cell carcinoma (42%) and control patients (19%).
  
  
  CONCLUSIONS
  The use of Tn antigen combined with DNA flow cytometry can increase tumour detection, particularly of high grade, aggressive disease. Gradation of expression of these markers across patient groups at increasing risk of a tumour, with intermediate expression in patients with no current tumour, suggests that marker expression may be detecting a preneoplastic stage of the disease, which is not possible with cytology. Given two parallel disease processes for superficial papillary and for high grade disease with invasive potential, the expression of high grade tumour markers in cells from cystoscopically normal bladders may represent a pre-clinical stage of aggressive disease. The identification of patients at risk of invasive disease using combinations of tumour markers may offer advantages in clinical management, particularly when no tumour is present and therefore no histopathological assessment is made.
authors.affiliation: Division of Surgery, Repatriation General Hospital Daw Park, South Australia.
authors.forename: C B
authors.initials: CB
authors.lastname: Pinnock
authors.forename: D J
authors.initials: DJ
authors.lastname: Roxby
authors.forename: J M
authors.initials: JM
authors.lastname: Ross
authors.forename: C H
authors.initials: CH
authors.lastname: Pozza
authors.forename: V R
authors.initials: VR
authors.lastname: Marshall
mesh_terms: D000368:Aged; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005819:Genetic Markers; D006801:Humans; D008297:Male; D011003:Ploidies; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D005819:Genetic Markers; C040286:Tn antigen