Frequent epigenetic silencing of the FHIT gene in penile squamous cell carcinomas

Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin (Impact Factor: 2.56). 05/2008; 452(4):377-82. DOI: 10.1007/s00428-008-0597-6
Source: PubMed

ABSTRACT Methylation of normally unmethylated CpG-rich islands in or near the promoter region has been associated with transcriptional inactivation of tumor-suppressor and tumor-related genes in human cancers. However, so far, only a few studies have searched for DNA methylation in penile carcinoma (PC). On the other hand, human papillomavirus (HPV) has been reported to be associated with the pathogenesis of PC. To elucidate the methylation status of PC and HPV infection, the methylation status of eight genes (DAPK, FHIT, MGMT, p14, p16, RAR-beta, RASSF1A, and RUNX3), the incidences of the HPV status, and the expression of Fhit protein were examined in 25 PCs. The frequencies of methylation were: 28% for DAPK, 92% for FHIT, 20% for MGMT, 4% for p14, 24% for p16, 24% for RAR-beta, 12% for RASSF1A, and 44% for RUNX3. Negative expression of Fhit protein was observed in 22 of the 25 cancers (88%). Among those 22, 20 showed methylation of the FHIT gene. HPV-DNA was detected in three of the 25 cancers (12%). Methylation of FHIT gene was frequently found than HPV infection, therefore methylation of the FHIT gene is suggested to play an important role in the pathogenesis of penile squamous cell carcinoma.

  • [Show abstract] [Hide abstract]
    ABSTRACT: ObjectiveTo investigate the relationship between fragile histidine triad (FHIT) depletion and human papillomavirus (HPV) status in the vulvar squamous cell carcinomas (VSCC). MethodsImmunohistochemical method was used to detect the expression of FHIT protein in 42 cases of VSCC and 10 cases of normal vulvar tissues. PCR was used to detect HPV infection status. We analyzed the relationship of the expression of FHIT protein between the 2 groups: HPV positive and HPV negative, as well as the clinically pathological characteristics. ResultsThe expression of FHIT was positive in all normal vulvar tissues, and 71.4% was depletion in VSCC (P < 0.01). Abnormal expression of FHIT was significantly correlated with pathological grade (P < 0.05). There was a significant diff erence between FHIT depletion and HPV infection based on the statistial analysis (P < 0.05). ConclusionThe FHIT depletion is related to occurrence and development of VSCC, and the abnormal expression of FHIT significantly correlates with HPV infection.
    Clinical Oncology and Cancer Research 02/2009; 6(1):68-71. DOI:10.1007/s11805-009-0068-0
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epigenetics is the study of differences in phenotype, in the absence of variation in the genetic code. Epigenetics is relevant in the pathogenesis of many skin diseases. In the case of the common skin cancers, aberrant methylation of tumor suppressor gene promoters is associated with their transcriptional inactivation. Environmental carcinogens such as ultraviolet radiation and arsenic may act through epigenetic mechanisms. Hypomethylation is associated with activation of systemic autoimmune diseases, such as systemic lupus erythematosus, subacute cutaneous lupus erythematosus and scleroderma. This may be through a mechanism of immunological cross-reactivity with hypomethylated DNA from pathogenic bacteria. Epigenetic factors may also be relevant in the pathogenesis of psoriasis and other inflammatory skin diseases, as well as in the pathogenesis of the disorders of genomic imprinting with cutaneous features.
    Pharmacogenomics 01/2009; 9(12):1835-50. DOI:10.2217/14622416.9.12.1835 · 3.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Penile carcinoma is an uncommon and potentially mutilating disease with a heterogeneous aetiology. Several risk factors have been established for its development. Human papillomavirus (HPV) infection seems to play an important role in the development of a subset of these carcinomas and its presence is thought to be related to the histological type. HPV prevalence in penile tumours is reported to be associated to a variety of morphological changes. Its determination will provide a better estimate for HPV related cancer burden and its preventable fraction. A systematic and comprehensive literature review of the major penile cancer studies published from 1986 until June 2008 evaluating the HPV prevalence among the different histological types was carried out. 31 studies including 1466 penile carcinomas were reviewed. Global HPV prevalence was 46.9%. Relative contribution was: HPV-16 (60.23%), HPV-18 (13.35%), HPV-6/11 (8.13%), HPV-31 (1.16%), HPV-45 (1.16%), HPV-33 (0.97%), HPV-52 (0.58%), other types (2.47%). Assessment of multiple infections contribution is limited due to study design. Basaloid and warty squamous cell carcinomas were the most frequent HPV-related histological types, but keratinising and non-keratinising subtypes also showed prevalence rates of around 50%. About half of the penile tumours were associated with HPV 16-18 with little presence of other genotypes. Research on the mechanisms behind penile carcinogenesis is warranted. Available HPV vaccines are likely to be effective in penile tumours.
    Journal of clinical pathology 09/2009; 62(10):870-8. DOI:10.1136/jcp.2008.063149 · 2.55 Impact Factor
Show more