Browsing by Subject "Retinoblastoma"
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- PublicationOpen AccessAltered patterns of RB expression define groups of soft tissue sarcoma patients with distinct biological and clinical behavior(Murcia : F. Hernández, 2006) Polsky, D.; Mastorides, S.; Kim, D.; Dudas, M.; Leon, L.; Leung, D.; Woodruff, J.M.; Brennan, M.F.; Osman, I.; Cordon-Cardo, C.Background: Function of the retinoblastoma tumor suppressor protein (pRB) may be compromised at a genetic level by gene loss or mutation or at a posttranslational level by hyperphosphorylation. In this study, we examined adult soft tissue sarcomas (ASTS) to determine if alterations of pRB were associated with distinct patterns of pRB expression and clinical outcome. Design: We investigated 86 ASTS patients using monoclonal antibodies that distinguish between hyperphosphorylated and underphosphorylated pRB products. We also used microsatellite analysis to investigate the genetic status of the RB locus. We correlated pRB alterations with proliferative activity, and with clinicopathological outcomes. Results: Altered patterns of pRB expression are common in ASTS occurring in 84% of cases, and it is significantly associated with proliferative activity (p<0.001). Patients whose tumors either lack expression of pRB, or express hyperphosphorylated forms of pRB, have poor survivals compared to patients whose tumors exhibit a normal, underphosphorylated pattern of pRB expression (p=0.03). In addition, 63% of cases lacking expression of pRB showed loss-of-heterozygosity at the locus Conclusions: Inactivation of pRB is common in adult STS, which may be due to either gene loss or posttranslational modification, namely hyperphosphorylation. Both mechanisms are associated with tumor cell proliferation and poor survival.
- PublicationOpen AccessExpression of the retinoblastoma-related p107 and Rb2/p130 genes in human placenta: an immunohistochemicaI study(Murcia : F. Hernández, 2001) Cavallotti, I.; De Luca, L.; D'Aponte, A.; De Falco, M.; Acanfora, F.; Visciano, M.L.; Gualdiero, L.; De Luca, B.; Baldi, A.; De Luca, A.It has been proposed that tumor suppressor genes may have a role in the mechanisms of proliferation and differentiation during human placental development. The Retinoblastoma gene family is a well known family of tumor suppressor genes. Many studies have pointed out a role of this family not only in cell cycle progression, but also during development and differentiation. On the light of these observations we have investigated the immunohistochemical expression pattern of the Retinoblastoma family members, p107 and Rb2/p130 in human placenta samples in first trimester and full-term placental sections. p107 and pRb2lp130 showed the most abundant expression levels during the first trimester of gestation and progressively declined to being barely detectable in the placenta by late gestation. These results indicate that the expression of the above genes is modulated during placental development and suggest a mechanism for controlling trophoblast proliferation.
- PublicationOpen AccessHeat shock proteins and survivin, Relationship and effects on proliferation index of retinoblastoma cells(Murcia : F. Hernández, 2008) Jiang, L.-B.; Liu, X.-Q.; Li, B.; He, X.-J.; Jin, Y.L.; Li, L.-Q.; Gao, F.; Wang, N.-L.Survivin and HSPs (heat shock proteins) are important anti-apoptotic proteins. However, limited research has been done regarding the collective effects of HSPs and survivin on the proliferative activities of RB cells. The purpose of this study was to narrow this gap by focusing on the expression of HSP70 and HSP90 and the interaction of these proteins with survivin. The proliferative activities of RB cells were analyzed by assessing the Ki-67 labeling index. Ki-67 recognizes a nuclear antigen expressed in all phases of the cell cycle except G(0) and early G(1), which makes it an excellent marker of cells in the proliferative phase. Immunohistochemical procedures were performed on retinal tissues from 43 RB patients who had undergone enucleation. Expression of HSP70, HSP90 and survivin was found in 65.12%, 86.05% and 62.79% of the cases respectively. No expression of any of these markers was found in normal retinal tissues. Expression of survivin was more frequent when HSP90 was detected than when HSP90 was not detected (P<0.05). The Ki-67 labeling index was higher in cases in which HSP90 or survivin was found than in cases in which neither protein was found (P<0.05). The Ki-67 labeling index was higher in cases positive for both HSP90 and survivin than in cases in which neither protein or only one protein was found (P<0.05). Expression of HSP70 neither correlated with that of survivin, nor had any significant effect on the Ki- 67 labeling index (P>0.05). Although expression of HSPs and survivin and the Ki-67 labeling index did not correlate with histopathologic typing of RB (P>0.05), our findings demonstrate that expression of HSP90 correlates with that of survivin in RB and the coexistence of survivin and HSP90 probably plays an important role in cellular proliferation in RB. Further work is indicated to clarify the role of these processes in progression of RB.
- PublicationOpen Accesslmmunohistochemical demonstration of neuronal and astrocytic markers and oncofoetal antigens in retinoblastomas(Murcia : F. Hernández, 1991) Antúnez, Jose R.; Couce, Marta; Fraga, Maximo; Garcia-Caballero, Tomas; Beiras, Andres; Perez-Becerra, Eugenio; Forteza, JeronimoGeneral opinion is that retinoblastomas, though not everyone agrees with that view. Some authors suggest that retinoblastomas are derived from a primitive retinal cell able to differentiate into both neuronal and glial cell lines. The aim of tlie present work was to study immunohistocheniically tlie expression of neuronal and astrocytic markers in retinoblastomas and at the same time the presence of tlie oncofoetal antigens carcinocnihryoiiic antigen (CEA) and alpha Focto Protein (AFP). since patients with retinoblastomas often show high oncofoctal antigen in serum levels. For this purpose we cnnployed the strcptavidin-biotin inimunopcroxidase technique in 13 cases of retinobla5toma to evaluate the presence ancl distribution of neuron-specific enolase (NSE). neurofilament protein (NF), glial fihrillary acidic piutein (GFAP), S-l00 protein. CEA and AFP. All 13 tumours \tudicd stained for NSE. Seven of them showed GFAP- and S-l00 positive per ivasc~~lgalri al cells as well as cells distributed randomly in the tuniour that were interpreted as non tumour cells. All 13 retinohlustomas lacked detectable NF, CEA, and AFP. These results \ ~ ~ p p o rtth e idea that retinoblastomas are neuronal tumour\. although retinal glial cells may become incorporated in the tumour and proliferate in response to the t u ~ ~ i o u