Pescarmona E, De Sanctis V, Pistilli A, Pacchiarotti A, Martelli M, Guglielmi C, Mandelli F, Baroni C D, Le Coco F
Department of Experimental Medicine and Pathology, Policlinico Umberto I, Rome, Italy.
J Pathol. 1997 Nov;183(3):281-6. doi: 10.1002/(SICI)1096-9896(199711)183:3<281::AID-PATH1134>3.0.CO;2-Z.
Bcl-6 (LAZ-3) and Bcl-2 gene rearrangements have been respectively reported in 20-35 per cent and 10-25 per cent of diffuse large B-cell lymphomas (DLBCLs). Although these genetic lesions have been associated with different clinical outcomes (i.e., more favourable in Bcl-6 rearranged cases and poorer in Bcl-2 rearranged cases), their prognostic significance is still controversial. In the present study, we have investigated by Southern blot analysis the Bcl-6 and Bcl-2 gene configuration in a series of 80 lymph nodes involved by well-characterized DLBCLs, histologically defined according to the REAL and the updated Kiel classifications. The molecular findings have been correlated with the clinical features at presentation and with response to therapy. The majority of cases (57/80 = 71.2 per cent) had a centroblastic morphology. Bcl-6 rearrangements were detected in 23/80 cases (28.8 per cent), and were similarly associated with centroblastic (18/57 = 31.6 per cent) or immunoblastic (3/11 = 27.3 per cent) histotypes. In contrast, Bcl-2 was found to be rearranged in only three cases of centroblastic lymphoma (3.8 per cent). No significant differences were found between Bcl-6 rearranged and germline cases, as far as the clinical features at presentation are concerned. Forty-one patients, in whom the lymph node biopsy was performed at diagnosis, could be evaluated for response to treatment and clinical outcome. Most of these cases (30/41 = 73.2 per cent) were nodal DLBCL, without extranodal site involvement. Analysis of the clinical outcome showed no statistically significant differences between Bcl-6 rearranged and Bcl-6 germline cases (actuarial overall survival 50 per cent vs. 48 per cent, event-free survival 45 per cent vs. 46 per cent, at 4 years). These findings confirm that Bcl-6 rearrangements are the most frequent genetic lesion in DLBCL. The incidence of Bcl-2 involvement in our series is significantly lower than the figures reported in other studies, mainly from North American countries, probably reflecting heterogeneous patient selection and/or epidemiological variability. Finally, our results suggest that no relevant clinical differences are observed between Bcl-6 rearranged and Bcl-6 germline cases, when nodal DLBCLs are considered.
据报道，在20%-35%的弥漫性大B细胞淋巴瘤（DLBCL）中分别存在Bcl-6（LAZ-3）和Bcl-2基因重排。尽管这些基因损伤与不同的临床结局相关（即Bcl-6重排的病例预后较好，Bcl-2重排的病例预后较差），但其预后意义仍存在争议。在本研究中，我们通过Southern印迹分析研究了80例经充分特征化的DLBCL累及的淋巴结中Bcl-6和Bcl-2基因构型，这些病例根据REAL分类法和更新后的Kiel分类法进行了组织学定义。分子研究结果与就诊时的临床特征以及治疗反应相关。大多数病例（57/80 = 71.2%）具有中心母细胞形态。在23/80例病例（28.8%）中检测到Bcl-6重排，其与中心母细胞型（18/57 = 31.6%）或免疫母细胞型（3/11 = 27.3%）组织学类型的关联相似。相比之下，仅在3例中心母细胞淋巴瘤病例（3.8%）中发现Bcl-2重排。就就诊时的临床特征而言，Bcl-6重排病例与种系病例之间未发现显著差异。41例在诊断时进行了淋巴结活检的患者可评估其治疗反应和临床结局。这些病例中的大多数（30/41 = 73.2%）为淋巴结DLBCL，无结外部位受累。临床结局分析显示，Bcl-6重排病例与Bcl-6种系病例之间无统计学显著差异（4年时精算总生存率分别为50%和48%，无事件生存率分别为45%和46%）。这些发现证实Bcl-6重排是DLBCL中最常见的基因损伤。我们研究系列中Bcl-2受累的发生率显著低于其他研究（主要来自北美国家）报道的数据，这可能反映了患者选择的异质性和/或流行病学差异。最后，我们的结果表明，当考虑淋巴结DLBCL时，Bcl-6重排病例与Bcl-6种系病例之间未观察到相关的临床差异。
