Retinoblastoma: Review and new insights.

Retinoblastoma (Rb), the most frequent malignant intraocular tumor in childhood, is caused by mutations in the retinoblastoma gene (RB1) situated on chromosome 13q14.2. The incidence of retinoblastoma is approximately 1 in 17,000 live births with approximately 8,000 new cases diagnosed each year worldwide. Rb is the prototypical hereditary cancer in humans. Autosomal dominant inheritance is seen in 30-40% of cases whereas the non-inherited sporadic type accounts for the remaining 60-70%. Rb arises due to inactivation of both alleles of the Rb tumor suppressor gene, which results in a defective Rb protein (pRB) with subsequent cell cycle impairment and uncontrolled cell proliferation. Patients with Rb have survival rates higher than 95-98% in industrialized countries but mortality remains high in developing countries. For example, the mortality rate in Africa is 70%. In all cases of intraocular and extraocular retinoblastoma, there is a need for new therapies that are more effective and carry less risk of toxicity. The Bruckner test is a practical and easy test for the detection of Rb, this test consists of assessing the fundus reflex through the pupil (red reflex) in both eyes simultaneously with a bright coaxial light produced with the direct ophthalmoscope. Rb can be detected by the Bruckner test showing a pupil that shines white or "Leukocoria". Although the diagnosis of Rb remains essentially clinical, the newly identified biomarkers could contribute to early molecular detection, timely detection of micrometastases and establish new therapeutic options for Rb.

Identification of DNA sequences and viral proteins of 6 human papillomavirus types in retinoblastoma tissue.

PURPOSE: To detect DNA and proteins of human papillomavirus (HPV) in paraffin-embedded retinoblastoma (RB) tissue, to identify the viral types present and to describe a possible association between the presence of HPV and a particular form of RB. MATERIALS AND METHODS: Fifty-one samples from ocular tissues of RB patients and of six controls enucleated for non-neoplastic reasons were obtained and analyzed by Polymerase Chain Reaction (PCR) with consensus primers to detect HPV. Viral type identification was performed by Restriction Fragment Length Polymorphisms (RFLP) analysis. To corroborate the presence of HPV, immunohistochemical analysis with a polyclonal anti-HPV antibody was performed in 10 RB cases and in all controls. RESULTS: Forty-two (82.3%) of the 51 samples were HPV-positive. HPV 6 was detected in 40 cases (95.2%), HPV 33 in 16 (38.1%), HPV 11 in 4 (9.5%) and HPV 31, 35 and 51 each in one case (2.3%). All controls were negative for HPV-DNA. The positive samples were PCR-tested for HPV 16 and 18 using specific primers, and were all negative. For immunohistochemical analysis, 7 out of 10 PCR-positive samples randomly chosen were positive; all six controls were negative. CONCLUSION: No differences in the HPV type distribution were found between the groups formed according to the tumor presentation or to the mode of inheritance.