Hostein Isabelle, Andraud-Fregeville Marie, Guillou Louis, Terrier-Lacombe Marie-José, Deminière Colette, Ranchère Dominique, Lussan Catherine, Longavenne Elisabeth, Bui Nguyen Binh, Delattre Olivier, Coindre Jean-Michel
Department of Pathology, Institut Bergonié, Bordeaux, France.
Cancer. 2004 Dec 15;101(12):2817-24. doi: 10.1002/cncr.20711.
Identification of the alveolar subtype of rhabdomyosarcoma (ARMS) is important, because the poor prognosis associated with this subtype necessitates a modified therapeutic regimen. At present, ARMS diagnoses are made on the basis of histologic findings and the extent of myogenin immunopositivity. Nonetheless, the absence of an alveolar pattern in the solid variant, the low degree of differentiation in certain embryonal rhabdomyosarcomas (ERMS), and the increasing use of microbiopsy samples make the diagnosis of ARMS somewhat difficult. Two specific translocations have been found in ARMS, and fusion transcripts can be detected by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of paraffin-embedded tissue (PET).
To assess the value of myogenin staining and molecular testing in the diagnosis of rhabdomyosarcoma, the authors examined 109 rhabdomyosarcoma samples (45 ARMS samples and 64 ERMS samples). Real-time RT-PCR analysis of PET was performed in all 109 rhabdomyosarcomas, and RT-PCR analysis of frozen material was performed in 24 cases.
PAX fusion transcripts were present in 44 cases (39 ARMS and 5 ERMS) and absent in 52 cases (2 ARMS and 50 ERMS). In 13 cases (4 ARMS and 9 ERMS), the results were not interpretable. Results were concordant between paired frozen and fixed tumor samples. All 35 interpretable ERMS samples that contained < 50% myogenin-positive cells failed to yield detectable PAX fusion transcripts. Of the 61 interpretable tumor samples (41 ARMS and 20 ERMS) that contained > 50% myogenin-positive cells, 44 (39 ARMS and 5 ERMS) yielded detectable PAX fusion transcripts.
The current study demonstrates that molecular detection of PAX fusion transcripts via real-time RT-PCR analysis of PET is a sensitive and specific method for the diagnosis of ARMS and that immunohistochemical analysis of myogenin expression can be used to select cases for such molecular testing. Although RT-PCR analysis appears not to possess diagnostic value in tumors with < 50% tumor cell immunopositivity, it is strongly recommended for the diagnosis of tumors containing > 50% myogenin-positive cells.
横纹肌肉瘤的肺泡型（ARMS）的识别很重要，因为该亚型预后较差，需要采用改良的治疗方案。目前，ARMS的诊断基于组织学发现和肌生成素免疫阳性程度。然而，实体变型中缺乏肺泡样结构、某些胚胎性横纹肌肉瘤（ERMS）的低分化程度以及微生物活检样本的使用增加，使得ARMS的诊断有些困难。在ARMS中发现了两种特定的易位，并且可以通过对石蜡包埋组织（PET）进行逆转录酶-聚合酶链反应（RT-PCR）分析来检测融合转录本。
为了评估肌生成素染色和分子检测在横纹肌肉瘤诊断中的价值，作者检查了109例横纹肌肉瘤样本（45例ARMS样本和64例ERMS样本）。对所有109例横纹肌肉瘤进行了PET的实时RT-PCR分析，并对24例进行了冷冻材料的RT-PCR分析。
44例（39例ARMS和5例ERMS）存在PAX融合转录本，52例（2例ARMS和50例ERMS）不存在。13例（4例ARMS和9例ERMS）结果无法解释。配对的冷冻和固定肿瘤样本结果一致。所有35例可解释的ERMS样本中，肌生成素阳性细胞<50%，均未产生可检测到的PAX融合转录本。在61例可解释的肿瘤样本（41例ARMS和20例ERMS）中，肌生成素阳性细胞>50%，其中44例（39例ARMS和5例ERMS）产生了可检测到的PAX融合转录本。
当前研究表明，通过对PET进行实时RT-PCR分析对PAX融合转录本进行分子检测是诊断ARMS的一种敏感且特异的方法，并且肌生成素表达的免疫组化分析可用于选择进行此类分子检测的病例。尽管RT-PCR分析在肿瘤细胞免疫阳性率<50%的肿瘤中似乎没有诊断价值，但强烈推荐用于诊断肌生成素阳性细胞>50%的肿瘤。
