Premium
Hypermethylation of the thrombospondin‐1 gene is associated with poor prognosis in penile squamous cell carcinoma
Author(s) -
Guerrero David,
Guarch Rosa,
Ojer Amaya,
Casas Juan Manuel,
Ropero Santiago,
Mancha Ana,
Pesce Carlo,
Lloveras Belen,
GarciaBragado Federico,
Puras Ana
Publication year - 2008
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2008.07603.x
Subject(s) - dna methylation , thrombospondin , cancer research , immunohistochemistry , methylation , penile carcinoma , biology , cd31 , penile cancer , epigenetics , thrombospondin 1 , cancer , pathology , gene , medicine , gene expression , angiogenesis , metalloproteinase , biochemistry , matrix metalloproteinase
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.