Yun K
Department of Pathology, University of Otago Medical School, Dunedin, New Zealand.
Lab Invest. 1992 Nov;67(5):653-64.
Accurate diagnosis of soft tissue tumors is often difficult and considered important because the clinical outcome and the modality of therapy vary according to tumor type. We have realized that rhabdomyoblasts seen in occasional Wilms' tumors express high levels of insulin-like growth factor II (IGF-II) transcripts. This observation prompted us to see if IGF-II could be a useful marker for differential diagnosis of rhabdomyosarcoma (RMS) from other soft tissue sarcomas.
Five cases of RMSs (including embryonal, botryoid, and alveolar types), various other soft tissue tumors, and 10-week gestation fetal muscle tissue were studied to demonstrate IGF-II transcripts by means of Northern blot hybridization and in situ mRNA hybridization using radio-labeled probes. Hybridization results were then compared with data obtained from immunohistochemistry using antibodies against desmin and vimentin.
Northern blot hybridization demonstrated that all five RMSs contained three major sizes of IGF-II transcripts. In situ hybridization indicated that all RMSs showed highly strong and specific IGF-II mRNA expression, whereas other soft tissue tumors showed very low or no signal. A characteristic finding was that the expression of IGF-II mRNA was inversely correlated with the degree of tumor cell differentiation. Thus poorly differentiated RMSs showed the highest signal, whereas well-differentiated RMSs showed low expression, albeit, still significantly higher than normal skeletal muscle fibers. Among five RMSs, desmin was seen in three tumors and vimentin in all tumors. Desmin was negative in other nonskeletal muscle origin tumors while vimentin was present in all tumors examined.
IGF-II has potential as a new marker for differential diagnosis of RMS from other soft tissue tumors and could be especially useful in differential diagnosis of small blue cell tumors.
软组织肿瘤的准确诊断往往困难且被认为很重要,因为临床结果和治疗方式会因肿瘤类型而异。我们已经认识到,偶见于肾母细胞瘤中的横纹肌母细胞表达高水平的胰岛素样生长因子II(IGF-II)转录本。这一观察结果促使我们探究IGF-II是否可作为从其他软组织肉瘤中鉴别诊断横纹肌肉瘤(RMS)的有用标志物。
研究了5例RMS(包括胚胎型、葡萄状和肺泡型)、各种其他软组织肿瘤以及妊娠10周的胎儿肌肉组织,通过Northern印迹杂交和使用放射性标记探针的原位mRNA杂交来检测IGF-II转录本。然后将杂交结果与使用抗结蛋白和波形蛋白抗体的免疫组织化学数据进行比较。
Northern印迹杂交表明,所有5例RMS均含有三种主要大小的IGF-II转录本。原位杂交显示,所有RMS均表现出高度强烈且特异性的IGF-II mRNA表达,而其他软组织肿瘤显示出非常低的信号或无信号。一个特征性发现是,IGF-II mRNA的表达与肿瘤细胞分化程度呈负相关。因此,低分化的RMS显示出最高信号,而高分化的RMS显示出低表达,尽管仍明显高于正常骨骼肌纤维。在5例RMS中,3例肿瘤中可见结蛋白,所有肿瘤中均可见波形蛋白。结蛋白在其他非骨骼肌起源的肿瘤中为阴性,而波形蛋白在所有检测的肿瘤中均存在。
IGF-II有潜力作为从其他软组织肿瘤中鉴别诊断RMS的新标志物,尤其在小蓝细胞肿瘤的鉴别诊断中可能有用。