CHEK2 germline mutations correlate with recurrence rate in patients with superficial bladder cancer.
BACKGROUND
Some bladder cancers can be the result of genetic predisposition or chromosomal abnormalities, but no clinical useful molecular marker exists to identify patients with higher risk ofrecurrence. We analyzed the recurrence rate in patients with three variants of tumor suppressor gene mutation, checkpoint kinase 2 (CHEK2). The endpoint of the study was to evaluate the rate, risk of recurrence and free-recurrence survival during 24-months observation time in CHEK2 positive (CHEK2+) and control group.


METHODS
The observation group consisted of 24 CHEK2+ patients among 445 treated on account of bladder cancer. Patients with > or = T2 and/or G3 disease were excluded from the study. Control group included 44 consecutive patients with superficial bladder cancer (SBC). Clinical data were collected from the patients' clinical records and correlated with chromosomal studies.


RESULTS
Tumor grade had no impact on risk of recurrence. Stage T1 revealed to be the strong recurrence predictor until 15th month of follow-up when compared to stage Ta. CHEK2 mutations strongly correlated (odds ratio = 6.47; p = 0.08) with the risk of recurrence comparing to T1 stage (OR = 1.49), and grade 2 (OR = 0.85). CHEK2 factor was also significant risk factor for the number of recurrences in particular periods of follow-up.


CONCLUSIONS
The results indicate that patients with CHEK2 mutation may present poorer clinical course with several recurrences of SBC. It also suggests a possible prognostic significance of CHEK2 analysis in identifying patients with higher risk of recurrence, which may imply more aggressive treatment modalities or necessity of modified follow-up schedule.
Katedra i Klinika Urologii Pomorskiej Akademii Medycznej w Szczecinie, Szczecin.
Marcin
M
Słojewski
Elzbieta
E
Złowocka
Cezary
C
Cybulski
Bohdan
B
Górski
Tadeusz
T
Debniak
Dominika
D
Wokołorczyk
Joanna
J
Matyjasik
Andrzej
A
Sikorski
Jan
J
Lubiński
D000368:Aged; D064447:Checkpoint Kinase 2; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016147:Genes, Tumor Suppressor; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases