ABSTRACT
ABSTRACT Purpose: The cellular origin of retinoblastoma is uncertain as constituent tumor cells heterogeneously express markers of both immature and mature retinal cells. An immunohistochemical analysis of cellular origin may yield valuable insights into disease progression and treatment options. This study aimed to determine the cellular origin of retinoblastoma in a large case series and correlate these findings with histopathological prognostic factors. Methods: Thirty-nine retinoblastoma cases were histopathologically diagnosed and analyzed by immunohistochemistry using monoclonal antibodies against the immature neural cell marker SRY-box containing gene 2 (SOX-2), the mature neuronal cell marker microtubule-associated protein 2 (MAP2), and the mature glial cell marker glial fibrillary acidic protein (GFAP). Histopathological features were also evaluated, including patterns of growth, differentiation, vitreous seeding, and choroidal/scleral, optic nerve, and anterior chamber invasion. Two retinoblastoma cell lines, WERI-1 and Y79, were studied by immunocytochemistry using the same antibodies. Results: Expression of SOX-2 was strong in 97.4% of retinoblastoma cases, while MAP-2 was expressed in 59% of cases. Immunostaining for GFAP was positive only in reactive stromal astrocytes interspersed amongst tumor cells and in peritumoral tissue. There was no correlation between histopathological prognostic factors and immunohistochemical markers. Retinoblastoma cell lines showed strong positivity for SOX2 (90% of WERI-1 cells and 70% of Y79 cells) and MAP2 (90% of cells in both lines). GFAP was completely negative in both cell lines. Conclusion: The majority of retinoblastomas and both RB cell lines expressed an immature neural and/or a mature neuronal cell marker, but not a glial marker. These results indicate a typical neuroblast or neuronal origin and eliminate astrocyte differentiation from neural stem cells as the source of retinoblastoma.
RESUMO Objetivos: Este estudo visa determinar a origem do retinoblastoma em um número de casos e correlacionar essos achados com fatores prognósticos e histopatológicos conhecidos. Métodos: Trinta e nove casos de retinoblastoma foram diagnosticados e analisados com imuno-histoquímica usando marcadores de anticorpos monoclonais contra as células de retina imaturas (SOX-2: SRY-box containing gene 2), contra as células da retina maturas (MAP2: microtubule -associated protein 2) e contra as células gliais maturas (GFAP: glial fibrillar acidic protein). Foram avaliadas características microscópicas dos casos (grau de diferenciação, presença de semeadura vítrea, invasão de coroide/esclera, nervo óptico e câmara anterior). Duas linhas celulares de retinoblastoma (WERI-1 e Y79) também foram testadas, utilizando os três marcadores. Resultados: A expressão de SOX-2 foi positiva em 97,4% dos casos de retinoblastoma, enquanto MAP2 foi positivo em 59% dos casos. GFAP foi apenas positivo no estroma (astrócitos reativos). Não houve correlação entre preditores histopatológicos e marcadores imunohistoquímicos avaliados. As linhagens celulares mostraram positividade para SOX-2 (90% em WERI-1 e 70% das células Y79). Ambas as linhagens celulares se mostraram fortemente positivas con MAP2 (90%), enquanto não houve expressão de GFAP em nenhuma das linhas celulares estudadas. Conclusões: A maioria das células de retinoblastoma desta série de casos expressa marcadores de células retinianas imaturas, além de marcadores de células maduras. As linhas celulares Y79 e WERI-1 apresentaram imunomarcação para ambos os marcadores neurais em percentagens semelhantes a dos casos avaliados. Portanto, estes resultados confirmam a origem neural do tumor em particular. Alem disso, a ausência de células positivas para GFAP no tumor descarta diferenciação de astrócitos em retinoblastoma.
Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Retinoblastoma/metabolism , Neuroglia/metabolism , Retinal Neoplasms/metabolism , Neural Stem Cells/pathology , Phenotype , Prognosis , Retinoblastoma/pathology , Immunohistochemistry , Biomarkers/metabolism , Neuroglia/pathology , Astrocytes/metabolism , Astrocytes/pathology , SOXB1 Transcription Factors/metabolism , Neural Stem Cells/metabolism , Glial Fibrillary Acidic Protein/metabolism , Microtubule-Associated Proteins/metabolism , Antibodies, Monoclonal/analysis , Antibodies, Monoclonal/metabolismABSTRACT
Ocular pathology is an important branch of histopathology,which plays a key role in understanding and revealing ocular diseases.In ophthalmology, retinoblastoma (RB) and uveal melanoma (UM) are common primary malignant intraocular neoplasms,which seriously endanger patients' lives.About two thirds of RB patients are caused by sporadic somatic mutations in the Rb1 gene,and the other one third of RB patients are caused by germline mutations in the Rb1 gene,which occur in the early age,are usually bilateral and transmissible to offsprings.High-risk histopathologic factors of RB mainly include the retrolaminar optic nerve invasion and/or massive choroidal invasion,and these are main indications for postoperative adjuvant chemotherapy.At present, due to lack of effective systemic therapy, about half of UM patients succumb to distant metastasis, most of which are hepatic metastases.Poor prognostic indicators of intraocular neoplasms include large tumor, ciliary body involvement, epithelioid cell type, extraocular diffusion,etc.Monosomy 3 and class 2 gene expression profile are currently accurate and objective prognostic indicators.
ABSTRACT
The authors report 52 cases (61 eyes) of leukokoria in children averaging 7. 7 years of age. Most of the cases(22 cases of 22 eyes, 42.3％) were caused by neoplasms, followed by congenital diseases in 12 cases (19 eyes, 23％), and other causes including traumas and inflammations. 44 cases were treated by surgi cal intervention and 8 cases by-conservative medication. The important causative diseases were discussed.