A Distinctive Subset of PEComas Harbors TFE3 Gene Fusions
A Distinctive Subset of PEComas Harbors TFE3 Gene Fusions
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DOI：
10.1097/pas.0b013e3181f17ac0
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发表时间：
2010-10-01
影响因子：
5.6
通讯作者：
Weiss, Sharon W.
中科院分区：
文献类型：
--
作者：
Argani, Pedram;Aulmann, Sebastian;Weiss, Sharon W.
血管周围上皮样细胞肿瘤（PEComa）包括常见的肾血管平滑肌脂肪瘤、肺透明细胞糖瘤、淋巴管平滑肌瘤病和较不常见的软组织、妇科和胃肠道肿瘤。最近，异常的免疫反应性TFE 3蛋白（一个敏感和特异性标记的肿瘤窝藏TFE 3基因融合）已报告在多达100%的PEComa，然而，TFE 3基因状态在这些肿瘤还没有系统地研究。我们使用了荧光原位杂交（FISH）分离分析，以评估TFE 3基因融合的证据，从29 PEComa档案材料。这些病例包括2例早期发表的TFE 3免疫反应性非肾性PEComa，14例其他非肾性PEComa和13例主要为梭形或上皮样形态的肾血管平滑肌脂肪瘤。4例非肾性PEComa（平均患者年龄24岁）通过FISH显示TFE 3基因重排，使用原始验证的过夜孵育方案，所有4例均显示强阳性（3+）TFE 3免疫反应性。其中两例有足够的mRNA进行RT-PCR分析，但都没有窝藏PSF-TFE 3基因融合早期报告的1 PEComa。此外，子宫PEComa的肺转移显示TFE 3基因扩增，这是一种早期未报道的现象。其他24例PEComa（平均患者年龄54岁）均未显示TFE 3基因改变，但4例显示中度阳性（2+）TFE 3免疫反应性。相比之下，使用自动染色机，这4例病例中的2例表现出强（3+）TFE 3免疫反应性。与其他PEComa相似，所有具有TFE 3基因改变的PEComa均强烈免疫标记组织蛋白酶K。总之，目前归类为PEComa的一部分病变具有TFE 3基因融合。虽然数量很少，但这些病例的显著特征包括倾向于年轻，与结节性硬化症无关，主要的肺泡结构和上皮样细胞学，肌肉标记物的免疫反应性极低，以及强（3+）TFE 3免疫反应性。尽管与其他PEComa有显著的形态学和免疫组化重叠，但携带TFE 3基因融合的PEComa可能代表一种独特的实体。
Perivascular epithelioid cell neoplasms (PEComas) include the common renal angiomyolipoma, pulmonary clear cell sugar tumor, lymphangioleiomyomatosis, and less common neoplasms of soft tissue, gynecologic, and gastrointestinal tracts. Recently, aberrant immunoreactivity for TFE3 protein (a sensitive and specific marker of neoplasms harboring TFE3 gene fusions) has been reported in as many as 100% of PEComas; however, TFE3 gene status in these neoplasms has not been systematically investigated. We used a fluorescence in situ hybridization (FISH) break-apart assay to evaluate for evidence of TFE3 gene fusions in archival material from 29 PEComas. These cases included 2 earlier published TFE3 immunoreactive nonrenal PEComas, 14 additional nonrenal PEComas, and 13 renal angiomyolipomas with predominantly spindle or epithelioid morphology. Four nonrenal PEComas (mean patient age 24 y) showed TFE3 gene rearrangements by FISH, and all 4 of these showed strong positive (3+) TFE3 immunoreactivity using the original validated overnight incubation protocol. Two of these cases had adequate mRNA for RT-PCR analysis, but neither harbored the PSF-TFE3 gene fusion reported earlier in 1 PEComa. In addition, a lung metastasis of a uterine PEComa showed TFE3 gene amplification, an earlier unreported phenomenon. None of the other 24 PEComas (mean patient age 54 y) showed TFE3 gene alterations, though 4 exhibited moderate positive (2+) TFE3 immunoreactivity. In contrast, using an automated stainer, 2 of these 4 cases exhibited strong (3+) TFE3 immunoreactivity. All PEComas with TFE3 genetic alterations immunolabeled strongly for Cathepsin K, similar to other PEComas. In conclusion, a subset of lesions currently classified as PEComas harbors TFE3 gene fusions. Although numbers are small, distinctive features of these cases include a tendency to young age, the absence of association with tuberous sclerosis, predominant alveolar architecture and epithelioid cytology, minimal immunoreactivity for muscle markers, and strong (3+) TFE3 immunoreactivity. Despite significant morphologic and immunohistochemical overlap with other PEComas, PEComas harboring TFE3 gene fusions may represent a distinctive entity.