ABSTRACT
Objective To observe the expression of matrix metalloproteinase(MMP-2, MMP-9 and vascular endothelial growth factor (VEGF) in retinoblastoma (RB) and its relationship with the differentiation and optic nerve infiltration of RB. Methods Forty paraffin specimens of pathological confirmed RB were studied. They were divided into differentiated group (15 cases) and undifferentiated group (25 cases) , optic nerve infiltration group( 13 cases) and without optic nerve infiltration group(27cases). The expression of MMP-2, MMP-9 and VEGF were detected by immunohistochemistry, their relationships with the differentiation and optic nerve infiltration were also analyzed. Results The positive rate of MMP-2, MMP-9 and VEGF expression in 40 RB cases were 52.5%, 57.5% and 72.5%respectively. The expression of MMP-2, MMP-9 and VEGF in the undifferentiated group were significantly higher than those in the differentiated group (χ2= 9. 037, 9. 253, 8. 095;P＜0. 05). The expression ofMMP-2, MMP-9 and VEGF in RB with optic nerve infiltration group were significantly higher than those in RB without optic nerve infiltration group (χ2=11.045,10. 243, 8. 956;P＜0. 05). The expression of MMP-2,MMP-9 had a positive correlation with the expression of VEGF in RB (r= 0. 126, 0. 314;P ＜ 0. 05).Conclusions MMP-2, MMP-9 and VEGF expressed in RB tumor tissues. The expression of MMP-2,MMP-9 has a positive correlation with the expression of VEGF. The levels of MMP-2, MMP-9 and VEGF expression are related to optic nerve infiltration of RB cells.
ABSTRACT
Children with retinoblastoma (RB) typically survive their cancer due to advances in early diagnosis and treatment. Extraocular invasion and metastasis, and secondary malignant tumor carry a very high mortality rate. Prerequisites for metastasis include tumor initiating capacity, altered cellular adhesion and cell motility, resistance to extracellular death signals and disruption of the basement membrane and extracellular matrix. All those changes can be determined by the cell of origin and the genetic instability of the tumor, responding to the multiple layers of pressure such as hypoxia, from the tumor microenvironment or niche. The interaction between tumor cells and the tumor stroma is regulated by several metastasissuppressor proteins and microRNA. This knowledge has important implications for our understanding and the treatment of extraocular spreading of RB.
ABSTRACT
The debate on the cell of origin of human retinoblastoma lasted for more than one century.In the recent issue of "cell",David Cobrinik's group shows that L/M cone precursors are the most likely answer as they have an intrinsic circuitry,including murine double minute 2 (MDM2),N-myc,the nuclear receptors retinoid X receptor and thyroxine receptor 2,making them extremely sensitive to transformation following retinoblastoma gene inactivation.