Assessing the use of p16(INK4a) promoter gene methylation in serum for detection of bladder cancer.
OBJECTIVE
This study was undertaken to investigate whether hypermethylation in p16(INK4a) gene promoter could serve as plasma biomarker of bladder cancer.


METHODS
We examined the p16(INK4a) status using methylation-specific PCR in 86 cancer patients and 49 controls (31 healthy people and 18 patients with benign urological diseases).


RESULTS
The p16(INK4a) methylation was found in 22% of the serum samples and in 26% of the bladder cancer biopsies; one of them with carcinoma in situ. The presence of hypermethylated p16(INK4a) in serum seems to be a product from tumour cells because a strong statistical association was found between both matched DNA signals (p<0.0001). Using the control group, the presence of methylated p16(INK4a) in the serum of individuals with suspicion of bladder cancer was found to be associated with the tumour presence (p=0.0009). Aberrant p16(INK4a) methylation was also observed in one non-cancer patient, which is undergoing further assessment.


CONCLUSIONS
According with our results, methylation of p16(INK4a) promoter may be involved in the bladder cancer genesis and the presence of p16(INK4a) methylated in serum of these patients could be useful in the cancer diagnosis with values of sensitivity, specificity and positive predictive value of 0.226, 0.950 and 0.98, respectively. These figures support the use of methylated p16(INK4a) as a new class of tumour marker in bladder cancer.
Valenzuela
M T
MT
Unidad Mixta de Investigaciones Médicas, Departamento de Radiología y Medicina Física, Hospital Universitario San Cecilio, Universidad de Granada, 18071 Granada, Spain.
Galisteo
R
R
Zuluaga
A
A
Villalobos
M
M
Núñez
M I
MI
Oliver
F J
FJ
Ruiz de Almodóvar
J M
JM
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16