Orellana María Eugenia, Belfort Rubens, Antecka Emilia, Burnier Miguel Noel
Ocular Pathology Section, Instituto Anatomopatológico "Dr. José A. O'Daly," Universidad Central de Venezuela, Caracas, Venezuela.
Ocular Oncology Sector, Department of Ophthalmology and Visual Sciences, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
Arq Bras Oftalmol. 2016 Nov-Dec;79(6):395-399. doi: 10.5935/0004-2749.20160111.
: 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.
: 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.
: 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.
: 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.
视网膜母细胞瘤的细胞起源尚不确定，因为组成肿瘤的细胞异质性地表达未成熟和成熟视网膜细胞的标志物。对细胞起源进行免疫组织化学分析可能会为疾病进展和治疗方案提供有价值的见解。本研究旨在确定一大组病例系列中视网膜母细胞瘤的细胞起源，并将这些发现与组织病理学预后因素相关联。
对39例视网膜母细胞瘤病例进行组织病理学诊断，并使用针对未成熟神经细胞标志物含SRY盒基因2（SOX-2）、成熟神经元细胞标志物微管相关蛋白2（MAP2）和成熟胶质细胞标志物胶质纤维酸性蛋白（GFAP）的单克隆抗体通过免疫组织化学进行分析。还评估了组织病理学特征，包括生长模式、分化、玻璃体播散以及脉络膜/巩膜、视神经和前房侵犯。使用相同抗体通过免疫细胞化学研究了两种视网膜母细胞瘤细胞系WERI-1和Y79。
SOX-2在97.4%的视网膜母细胞瘤病例中表达强烈，而MAP-2在59%的病例中表达。GFAP免疫染色仅在散布于肿瘤细胞之间的反应性基质星形胶质细胞和肿瘤周围组织中呈阳性。组织病理学预后因素与免疫组织化学标志物之间无相关性。视网膜母细胞瘤细胞系对SOX2（WERI-1细胞的90%和Y79细胞的70%）和MAP2（两种细胞系中90%的细胞）呈强阳性。两种细胞系中GFAP均完全阴性。
大多数视网膜母细胞瘤以及两种视网膜母细胞瘤细胞系均表达未成熟神经和/或成熟神经元细胞标志物，但不表达胶质标志物。这些结果表明其典型的神经母细胞或神经元起源，并排除了神经干细胞的星形胶质细胞分化作为视网膜母细胞瘤的来源。
