Ex vivo chemosensitivity to mitomycin C in bladder cancer and its relationship with P-glycoprotein and apoptotic factors.
BACKGROUND
Intravesical treatment with mitomycin C (MMC) leads to a complete response rate of around 40% in superficial bladder cancer (TCC). In order to determine in advance which patients will fail to respond, we describe a study assessing the feasibility of applying the ATP assay to test the chemosensitivity of samples from patients with this disease.


METHODS
TURBT or biopsy samples were received from 27 patients, 23 of which were suitable for the ATP assay (16 primary tumours and 7 recurrences).


RESULTS
The success rate of the assay was 91%. There was a marked variation in the effect of MMC between patients with a > 50-fold range in LC50 values (drug concentration required to kill 50% of cells) from 2.99- > 150 microM with a median value of 22.4 microM. We were unable to determine any overall correlation between chemosensitivity and tumour stage or grade or the treatment status of the patient in this small data set. P-glycoprotein status and caspase-3 levels were assessed on these samples using immunohistochemistry but there did not appear to be any relationship between either of these parameters and MMC resistance. Apoptotic counts and mitotic counts were also measured but, whilst these appeared to correlate with grade (p < 0.01), there was no overall significant relationship established with MMC chemosensitivity.


CONCLUSIONS
This study suggests that it is possible to use the ATP assay for chemosensitivity testing in TCCs. Despite a lack of overall correlation between ex vivo MMC resistance and the conventional prognostic factors tested, further studies are warranted in a larger data set to test the ability of this technique to predict clinical outcome in this disease.
Gontero
Paolo
P
Clinica Urologica, Dipartmento di Scienze Mediche, Università del Piemonto Orientale, Novara, Italy. paolo.gontero@med.unipmn.it
Sargent
Jean M
JM
Hopster
Debbie J
DJ
Lewandowic
G M
GM
Taylor
Colin G
CG
Elgie
Ann W
AW
Williamson
Carl J
CJ
Sriprasad
Sesadri I
SI
Muir
Gordon H
GH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000255:Adenosine Triphosphate / Q000032:analysis; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D008163:Luminescent Measurements; D008875:Middle Aged; D016685:Mitomycin / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects; D009336:Necrosis; D009367:Neoplasm Staging; D010865:Pilot Projects; D013778:Tetrazolium Salts; D013844:Thiazoles; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D013778:Tetrazolium Salts; D013844:Thiazoles; D016685:Mitomycin; D000255:Adenosine Triphosphate; C022616:thiazolyl blue