Collins M H, Zhao H, Womer R B, Barr F G
Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Med Pediatr Oncol. 2001 Aug;37(2):83-9. doi: 10.1002/mpo.1174.
Most alveolar rhabdomyosarcomas (ARMS) have chromosome translocations and resultant gene fusion products. The more common translocation fuses the PAX3 and FKHR genes; patients who have PAX3-FKHR-positive ARMS have reduced event-free survival compared to patients with ARMS containing the less common translocation that fuses the PAX7 and FKHR genes.
We examined histology, immunohistochemical markers of differentiation, and cell cycle characteristics of a panel of ARMS containing either PAX3-FKHR or PAX7-FKHR transcript to determine if these features differ between the ARMS subsets.
Cell cycle parameters varied significantly: the number of nuclei that stained with either an immunohistochemical marker of proliferation (MIB1), or a TUNEL-based assay for apoptosis was significantly greater in tumors that expressed PAX3-FKHR compared to tumors that expressed PAX7-FKHR transcript.
We conclude that compared to PAX7-FKHR-containing tumors, ARMS that contain PAX3-FKHR transcript have (1) increased cell proliferation, consistent with greater loss of cell cycle regulation, and (2) apoptosis that is increased but insufficient to prevent tumor formation. More marked cell cycle dysregulation may contribute to poorer prognosis for patients with ARMS that have PAX3-FKHR fusion. Med Pediatr Oncol 2001;37:83-89.
大多数肺泡横纹肌肉瘤（ARMS）存在染色体易位及由此产生的基因融合产物。较常见的易位是融合PAX3和FKHR基因；与含有较罕见的融合PAX7和FKHR基因易位的ARMS患者相比，PAX3 - FKHR阳性的ARMS患者无事件生存期缩短。
我们检测了一组含有PAX3 - FKHR或PAX7 - FKHR转录本的ARMS的组织学、免疫组化分化标志物及细胞周期特征，以确定这些特征在ARMS亚组间是否存在差异。
细胞周期参数差异显著：与表达PAX7 - FKHR转录本的肿瘤相比，表达PAX3 - FKHR的肿瘤中，用增殖免疫组化标志物（MIB1）或基于TUNEL的凋亡检测法染色的细胞核数量显著更多。
我们得出结论，与含有PAX7 - FKHR的肿瘤相比，含有PAX3 - FKHR转录本的ARMS有：（1）细胞增殖增加，这与细胞周期调控的更大程度丧失一致；（2）凋亡增加但不足以阻止肿瘤形成。更明显的细胞周期失调可能导致具有PAX3 - FKHR融合的ARMS患者预后更差。《医学与儿科肿瘤学》2001年；37:83 - 89。
