Department for Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinča, University of Belgrade, Mike Alasa 12-14, 11000, Belgrade, Serbia.
Med Oncol. 2013;30(3):682. doi: 10.1007/s12032-013-0682-9. Epub 2013 Aug 6.
Liposarcoma represents the most frequent group of soft tissue sarcomas. The group can be divided into three different classes: (1) differentiated/undifferentiated (WDLPS/DDLPS), (2) myxoid/round cell (MLPS/RCLPS) and (3) pleomorphic liposarcoma (PLS). It has become apparent that p53-p14 and Rb-p16 pathways play important roles in the pathogenesis of various sarcoma types. Molecular studies of the genes involved in these two pathways showed wide variations between the liposarcoma subtypes or even within the same subtype. We sought to examine mutational status of p53 and methylation status of p16 (INK4a) /p14 (ARF) genes in primary and recurrent liposarcoma tumors. There were twelve myxoid (12/18, 66.7 %) and six pleomorphic liposarcoma (6/18, 33.3 %) samples. Immunohistochemical analysis revealed that p53 protein was overexpressed in 3/12 MLPS (25 %) and 6/6 PLS (100 %). Mutational analysis showed that 2/11 MLPS (18.2 %) and 2/6 PLS (33.3 %) contained mutated p53 gene. On the other hand, 3/18 samples (16.7 %) had methylated p16 promoter. However, the frequencies of the p14 (ARF) gene methylation were 83.3 % (10/12) and 50 % (3/6) in myxoid and pleomorphic group, respectively. Overall, 15 out of 18 (83.3 %) samples had either p53 gene mutation or methylated p14 (ARF) promoter. The results from the current study suggest significant impact of the p14 (ARF) gene methylation on the pathogenesis and progression of myxoid and to a lesser extent pleomorphic liposarcoma. Despite the limited number of samples, our study points to necessity of further investigation of p53-p14 and Rb-p16 pathways in liposarcoma.
脂肪肉瘤是最常见的软组织肉瘤。该组可分为三类:(1)分化/未分化(WDLPS/DDLPS),(2)黏液样/圆形细胞(MLPS/RCLPS)和(3)多形性脂肪肉瘤(PLS)。很明显,p53-p14 和 Rb-p16 途径在各种肉瘤类型的发病机制中起着重要作用。对这两个途径中涉及的基因的分子研究表明,脂肪肉瘤亚型之间甚至在同一亚型内存在广泛的变异。我们试图检查原发性和复发性脂肪肉瘤肿瘤中 p53 的突变状态和 p16(INK4a)/p14(ARF)基因的甲基化状态。有 12 例黏液样(12/18,66.7%)和 6 例多形性脂肪肉瘤(18/18,33.3%)样本。免疫组织化学分析显示,在 3/12 MLPS(25%)和 6/6 PLS(100%)中 p53 蛋白过度表达。突变分析显示,在 2/11 MLPS(18.2%)和 2/6 PLS(33.3%)中含有突变的 p53 基因。另一方面,有 3/18 个样本(16.7%)的 p16 启动子甲基化。然而,在黏液样和多形性组中,p14(ARF)基因甲基化的频率分别为 83.3%(10/12)和 50%(3/6)。总的来说,18 个样本中有 15 个(83.3%)存在 p53 基因突变或 p14(ARF)启动子甲基化。目前的研究结果表明,p14(ARF)基因甲基化对黏液样和多形性脂肪肉瘤的发病机制和进展有显著影响。尽管样本数量有限,但我们的研究表明有必要进一步研究脂肪肉瘤中的 p53-p14 和 Rb-p16 途径。