Sullivan Lisa M, Atkins Kristen A, LeGallo Robin D
Department of Pathology, University of Virginia, Charlottesville, VA, USA.
Am J Surg Pathol. 2009 May;33(5):775-80. doi: 10.1097/PAS.0b013e318191614f.
PAX5 is a member of the paired box transcription factors involved in development and its expression has been well characterized among hematopoietic malignancies of B-cell lineage. Its expression has also been reported in a subset of neuroendocrine carcinomas, urothelial tumors, Merkel cell carcinoma, glioblastoma, and neuroblastoma cell lines. As such, we sought to assess it as a diagnostic marker in the evaluation of pediatric small round blue cell tumors. Tumors selected for evaluation included embryonal rhabdomyosarcoma (55 cases), alveolar rhabdomyosarcoma (ARMS) (51 cases), neuroblastoma (22 cases), Wilms tumor (18 cases), Ewing Family of Tumors (11 cases), lymphoblastic lymphoma (8 cases), hepatoblastoma (6 cases), and granulocytic sarcoma (3 cases) as either cores in a tissue microarray or whole mount sections. All cases were immunostained using an antibody directed toward PAX5 and immunoreactivity was scored semiquantitatively according to percentage of nuclear staining. As expected, all B-cell lymphoblastic lymphomas were strongly immunoreactive against PAX5. Additionally, all Wilms tumors showed staining of variable intensity, most intensely in the epithelial component. Of the rhabdomyosarcoma cases, 34 of 51 (67%) ARMS were immunoreactive whereas none of the 55 embryonal rhabdomyosarcoma cases stained. No other tumor type on the array was immunoreactive toward PAX5. Genetic information was available on 7 ARMS, 5 of which had characteristic translocations involving PAX genes, either t(2:13) or t(1;13). Of the translocation-positive cases, all showed nuclear reactivity toward PAX5, and both the translocation-negative cases did not. Possible explanations of PAX5 staining include aberrant expression of the PAX5 transcription factor, PAX5 expression in normal tissue at the time the tumors most closely recapitulates in development or crossreactivity with another member of the PAX family. PAX3 and PAX7 fusion genes characterize the majority of ARMS making crossreactivity with these proteins an attractive theory, and suggest that PAX5 immunoreactivity may be specific for translocation-positive ARMS. Further study in a larger series of rhabdomyosarcomas is warranted to assess the sensitivity and specificity of PAX5 immunoreactivity for the ARMS variant.
PAX5是配对盒转录因子家族的成员，参与细胞发育过程，其在B细胞系造血系统恶性肿瘤中的表达已得到充分研究。据报道，它也在一部分神经内分泌癌、尿路上皮肿瘤、默克尔细胞癌、胶质母细胞瘤和成神经细胞瘤细胞系中表达。因此，我们试图评估其作为小儿小圆蓝细胞肿瘤诊断标志物的价值。用于评估的肿瘤包括胚胎性横纹肌肉瘤（55例）、肺泡状横纹肌肉瘤（ARMS）（51例）、神经母细胞瘤（22例）、肾母细胞瘤（18例）、尤因家族性肿瘤（11例）、淋巴细胞性淋巴瘤（8例）、肝母细胞瘤（6例）和粒细胞肉瘤（3例），这些肿瘤均以组织芯片的核心或整装切片形式进行研究。所有病例均使用针对PAX5的抗体进行免疫染色，并根据核染色百分比进行半定量评分。正如预期的那样，所有B细胞淋巴细胞性淋巴瘤对PAX5均呈强免疫反应性。此外，所有肾母细胞瘤均显示出不同强度的染色，在上皮成分中染色最强。在横纹肌肉瘤病例中，51例ARMS中有34例（67%）呈免疫反应性，而55例胚胎性横纹肌肉瘤病例均未染色。芯片上的其他肿瘤类型对PAX5均无免疫反应性。7例ARMS有基因信息，其中5例有涉及PAX基因的特征性易位，即t(2;13)或t(1;13)。在易位阳性病例中，所有病例均显示对PAX5的核反应性，而两个易位阴性病例则未显示。PAX5染色的可能解释包括PAX5转录因子的异常表达、肿瘤在发育过程中最接近正常组织时PAX5在正常组织中的表达或与PAX家族另一成员的交叉反应。PAX3和PAX7融合基因是大多数ARMS的特征，与这些蛋白的交叉反应是一个有吸引力的理论，并表明PAX5免疫反应性可能对易位阳性的ARMS具有特异性。有必要对更多系列的横纹肌肉瘤进行进一步研究，以评估PAX5免疫反应性对ARMS变异型的敏感性和特异性。
