Cesarman E, Chadburn A, Liu Y F, Migliazza A, Dalla-Favera R, Knowles D M
Department of Pathology, The New York Hospital-Cornell Medical Center, New York, NY 10021, USA.
Blood. 1998 Oct 1;92(7):2294-302.
Posttransplantation lymphoproliferative disorders (PT-LPDs) represent a heterogeneous group of Epstein-Barr virus-associated lymphoid proliferations that arise in immunosuppressed transplant recipients. Some of these lesions regress after a reduction in immunosuppressive therapy, whereas some progress despite aggressive therapy. Morphological, immunophenotypic, and immunogenotypic criteria have not been useful in predicting clinical outcome. Although structural alterations in oncogenes and/or tumor suppressor genes identified in some PT-LPDs correlate with a poor clinical outcome, the presence of these alterations has not been a consistently useful predictor of lesion regression after reduction of immunosuppression. We examined 57 PT-LPD lesions obtained from 36 solid organ transplant recipients for the presence of mutations in the BCL-6 proto-oncogene using single-strand conformation polymorphism and sequence analysis, followed by correlation with histopathologic classification and clinical outcome, which was known in 33 patients. BCL-6 gene mutations were identified in 44% of the specimens and in 44% of the patients; none were identified in the cases classified as plasmacytic hyperplasia. However, mutations were present in 43% of the polymorphic lesions and 90% of the PT-LPDs diagnosed as non-Hodgkin's lymphoma or multiple myeloma. BCL-6 gene mutations predicted shorter survival and refractoriness to reduced immunosuppression and/or surgical excision. Our results suggest that the BCL-6 gene structure is a reliable indicator for the division of PT-LPDs into the biological categories of hyperplasia and malignant lymphoma, of which only the former can regress on immune reconstitution. The presence of BCL-6 gene mutations may be a useful clinical marker to determine whether reduction in immunosuppression should be attempted or more aggressive therapy should be instituted.
移植后淋巴组织增生性疾病（PT-LPDs）是一组异质性的、与爱泼斯坦-巴尔病毒相关的淋巴组织增生，发生于免疫抑制的移植受者。其中一些病变在免疫抑制治疗减量后会消退，而一些病变尽管接受了积极治疗仍会进展。形态学、免疫表型和免疫基因型标准在预测临床结果方面并无帮助。尽管在一些PT-LPDs中发现的癌基因和/或肿瘤抑制基因的结构改变与不良临床结果相关，但这些改变的存在并非始终是免疫抑制减量后病变消退的有用预测指标。我们使用单链构象多态性和序列分析，检测了36例实体器官移植受者的57个PT-LPD病变中BCL-6原癌基因的突变情况，随后将其与组织病理学分类和临床结果进行相关性分析，33例患者的临床结果已知。在44%的标本和44%的患者中检测到BCL-6基因突变；在分类为浆细胞增生的病例中未检测到突变。然而，在43%的多形性病变和90%被诊断为非霍奇金淋巴瘤或多发性骨髓瘤的PT-LPDs中存在突变。BCL-6基因突变预示着生存期缩短以及对免疫抑制减量和/或手术切除治疗无效。我们的结果表明，BCL-6基因结构是将PT-LPDs分为增生性和恶性淋巴瘤生物学类别的可靠指标，其中只有前者可在免疫重建后消退。BCL-6基因突变的存在可能是一个有用的临床标志物，用于确定是否应尝试减少免疫抑制或应采取更积极的治疗。
