Prognostic significance of survivin-expressing circulating tumour cells in T1G3 bladder cancer.
OBJECTIVE
To evaluate the prognostic significance of survivin in tumour tissues and that of survivin-expressing circulating tumour cells (CTCs) in T1G3 bladder tumours, as the prognosis of T1G3 bladder cancer is highly variable and unpredictable from clinical and pathological prognostic factors.


METHODS
The study included 54 patients with T1G3 non-muscle-invasive bladder cancer. Additional inclusion criteria were: tumour size <3 cm, absence of carcinoma in situ and multifocality. The planned follow-up was 24 months. Survivin was evaluated by reverse transcription-polymerase chain reaction in tumour tissues. CTCs were isolated from blood by CELLection Dynabeads (Invitrogen, Carlsbad, CA, USA) coated with the monoclonal antibody towards the human epithelial cell adhesion molecule. Cells were lysed and Dynabeads Oligo(dT) was used to capture poly A + mRNA. cDNA was synthesized and analysed for the expression of CD45, CK8 and survivin. The primary endpoint was disease-free survival (DFS); the favourable group at 24 months was defined as that with no clinical evidence of disease; the unfavourable group was that with evidence of recurrent disease or progressive disease. Tumour survivin expression and presence of CTC were correlated with DFS. Multivariate analysis was used to investigate whether the presence of CTC was an independent indicator of DFS.


RESULTS
Survivin was found in half of the tumours; patients with survivin-negative tumours had a longer DFS than those with survivin-positive tumours (chi-square, P = 0.029). CTCs were found in 24/54 patients (44%); 92% of CTC expressed survivin. The difference in DFS between CTC-ve and CTC+ve patients was statistically significant (chi-square, P < 0.001). The presence of CTC was an independent prognostic factor for DFS (P < 0.001).


CONCLUSIONS
The presence of CTC is an independent prognostic factor in patients with T1G3 bladder cancer.
Dipartimento Medicina Sperimentale, Sapienza Università di Roma, Rome, Italy.
Angela
A
Gradilone
Arianna
A
Petracca
Chiara
C
Nicolazzo
Walter
W
Gianni
Enrico
E
Cortesi
Giuseppe
G
Naso
Bruno
B
Vincenzi
Cristiano
C
Cristini
Ettore
E
De Berardinis
Franco
F
Di Silverio
Anna Maria
AM
Aglianò
Paola
P
Gazzaniga
D004812:Epidemiologic Methods; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology*
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin