Cb. Pinnock et al., PLOIDY AND TN-ANTIGEN EXPRESSION IN THE DETECTION OF TRANSITIONAL-CELL NEOPLASIA IN NON-TUMOR-BEARING PATIENTS, British Journal of Urology, 75(4), 1995, pp. 461-469
Objective To study the effectiveness of combining DNA ploidy and the b
lood-group related membrane antigen Tn as bladder tumour markers which
have been individually associated with high tumour grade and poor pro
gnosis. In particular to (i) determine whether use of these two marker
s would improve tumour detection compared with either alone, particula
rly of high grade disease and (ii) determine whether intermediate rate
s of marker expression would occur in bladder cancer patients with no
current tumour compared with those with a tumour and a control group w
ith benign prostatic hypertrophy. Patients and methods A total of 102
patients undergoing cystoscopic monitoring for either benign prostatic
hyperplasia (BPH) or for transitional cell carcinoma (TCC) at the Rep
atriation Hospital and Flinders Medical Centre were included in the st
udy. 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 tu
mour present at cystoscopy (n = 27). Exfoliated cells obtained from bl
adder washings at cystoscopy were double-labelled using a monoclonal a
ntibody to the Tn antigen and a DNA stain, propidium iodide and examin
ed by now 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 g
rade, 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 b
ut no current tumour, rates were intermediate (30%) compared with pati
ents with current transitional cell carcinoma (42%) and control patien
ts (19%). Conclusion The use of Tn antigen combined with DNA flow cyto
metry can increase tumour detection, particularly of high grade, aggre
ssive disease. Gradation of expression of these markers across patient
groups at increasing risk of a tumour, with intermediate expression i
n patients with no current tumour, suggests that marker expression may
be detecting a preneoplastic stage of the disease, which is not possi
ble with cytology. Given two parallel disease processes for superficia
l papillary and for high grade disease with invasive potential, the ex
pression of high grade tumour markers in cells from cystoscopically no
rmal bladders may represent a pre-clinical stage of aggressive disease
. The identification of patients at risk of invasive disease using com
binations of tumour markers may offer advantages in clinical managemen
t, particularly when no tumour is present and therefore no histopathol
ogical assessment is made.