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BJU Int. 2008 Sep;102(6):747-55. doi: 10.1111/j.1464-410X.2008.07603.x. Epub 2008 Mar 10.

Hypermethylation of the thrombospondin-1 gene is associated with poor prognosis in penile squamous cell carcinoma.

Author information

1
Biomedical Research Center, Navarra Health Service, Pamplona, Navarra, Spain. dguerres@cfnavarra.es

Abstract

OBJECTIVE:

To evaluate the presence of human papillomavirus (HPV) infection, the methylation status in the promoter region of thrombospondin-1 (TSP-1), RAS association domain family 1A (RASSF1-A) and p16 genes, and the expression of TSP-1, CD31, p16 and p53 proteins in patients diagnosed with penile cancer, and the possible associations between these variables and clinical and pathological features.

PATIENTS AND METHODS:

HPV types, gene promoter hypermethylation and protein expression were analysed by reverse line blot, methylation-specific polymerase chain reaction, and immunohistochemistry, respectively, in 24 penile squamous cell carcinomas.

RESULTS:

HPV infection was detected in 11 of 24 cases (46%), and TSP-1, RASSF1-A and p16 genes were hypermethylated in 46%, 42% and 38% of the tumours, respectively. TSP-1 hypermethylation was associated with unfavourable histological grade (grade 3; P = 0.033), vascular invasion (P = 0.023), weak expression of TSP-1 protein (P = 0.041), and shorter overall survival (P = 0.04). TSP-1 expression was not associated with microvessel density. However, RASSF1-A hypermethylation was more frequent in T1 tumours (P = 0.01), and p16 hypermethylation was not associated with any of the tested variables except for absence of p16 expression (P = 0.022).

CONCLUSION:

In summary, the epigenetic inactivation of TSP-1 and RASSF1-A genes is associated with pathological variables and seems to be of prognostic significance in penile cancer.

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