Machado Isidro, Noguera Rosa, Pellin Antonio, Lopez-Guerrero Jose A, Piqueras Marta, Navarro Samuel, Llombart-Bosch Antonio
Department of Pathology, University of Valencia, Valencia, Spain.
Diagn Mol Pathol. 2009 Dec;18(4):189-99. doi: 10.1097/PDM.0b013e3181a06f66.
To compare the sensitivity and specificity of fluorescence in situ hybridization (FISH) with reverse transcription polymerase chain reaction (RT-PCR) in the diagnosis of Ewing sarcoma family of tumors (ESFTs) and other small round-cell tumors (SRCTs) in formalin-fixed paraffin-embedded tissue assembled in tissue microarrays (TMAs). The second objective is to confirm the value of molecular methods and immunohistochemical (IHC) assays, to perform a differential diagnosis between ESFTs and SRCTs with similar or overlapping morphology.
A total of 560 cases were selected for the present study out the 806 cases collected from the PROgnosis and THerapeutic Targets in the Ewing's Family of TumorS project. Case selection bias included only the cases with enough material to enable the TMA construction, as FISH analysis and the majority of IHC studies were performed in TMAs. Histopathologic, IHC, and molecular assays were carried out.
Of the 560 total cases, 411 (73.4%) were considered informative (with results by FISH and/or RT-PCR assays). From the informative cases, 382 (92.9%) were diagnosed as ESFT, 23 cases (5.6%) as non-ESFT but with specific diagnosis for another established entity, and 6 cases (1.5%) as small round cell tumors not otherwise specified. Sensitivity and specificity for the FISH assays was 96.3% and 95.2%, respectively, whereas RT-PCR presented a sensitivity of 97.5% and specificity of 92.9%. In concordant cases, both methods showed a sensitivity and specificity of 99.2% and 100%, respectively. Twenty-nine cases (7.1%) initially interpreted at morphologic level as atypical ESFTs were finally reclassified, with the support of molecular methods and IHC, as either non-ESFT with another specific histologic type or as small round cell tumors not otherwise specified.
FISH and RT-PCR are ancillary techniques possessing high sensitivity in the diagnosis of ESFT; nevertheless, FISH is more specific than RT-PCR in the diagnosis of formalin-fixed paraffin-embedded tissue. Both methods in combination displayed the highest sensitivity and specificity. The combination of histopathologic, IHC, and molecular findings is the method of choice for the diagnosis of ESFT, as well as for the differential diagnosis with other SRCTs.
比较荧光原位杂交（FISH）与逆转录聚合酶链反应（RT-PCR）在诊断组织微阵列（TMA）中福尔马林固定石蜡包埋组织的尤因肉瘤家族肿瘤（ESFT）和其他小圆细胞肿瘤（SRCT）时的敏感性和特异性。第二个目的是确认分子方法和免疫组织化学（IHC）检测的价值，以对形态相似或重叠的ESFT和SRCT进行鉴别诊断。
从尤因肿瘤家族预后与治疗靶点项目收集的806例病例中，共选取560例用于本研究。病例选择偏倚仅包括有足够材料进行TMA构建的病例，因为FISH分析和大多数IHC研究均在TMA中进行。进行了组织病理学、IHC和分子检测。
在560例病例中，411例（73.4%）被认为信息充足（有FISH和/或RT-PCR检测结果）。在信息充足的病例中，382例（92.9%）被诊断为ESFT，23例（5.6%）为非ESFT但对另一个已确定的实体有明确诊断，6例（1.5%）为未另行特指的小圆细胞肿瘤。FISH检测的敏感性和特异性分别为96.3%和95.2%，而RT-PCR的敏感性为97.5%，特异性为92.9%。在一致的病例中，两种方法的敏感性和特异性分别为99.2%和100%。29例（7.1%）最初在形态学水平上被解释为非典型ESFT的病例，最终在分子方法和IHC的支持下，被重新分类为具有另一种特定组织学类型的非ESFT或未另行特指的小圆细胞肿瘤。
FISH和RT-PCR是在ESFT诊断中具有高敏感性的辅助技术；然而，在福尔马林固定石蜡包埋组织的诊断中，FISH比RT-PCR更具特异性。两种方法联合使用显示出最高的敏感性和特异性。组织病理学、IHC和分子检查结果相结合是ESFT诊断以及与其他SRCT进行鉴别诊断的首选方法。
