Anatomical Pathology, National Health Laboratory Service, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Clinical Haematology Unit, Department of Medicine, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa..
Ann Diagn Pathol. 2022 Jun;58:151913. doi: 10.1016/j.anndiagpath.2022.151913. Epub 2022 Feb 10.
Diffuse large B-cell lymphoma (DLBCL) comprises up to 43% of non-Hodgkin lymphomas in South Africa due to the high seroprevalence of human immunodeficiency virus (HIV) infection in the southern African region. We explored the prognostic influence of an array of clinicopathological factors, including MYC gene copy numbers, within HIV-associated DLBCL.
The retrospective inclusion of 123 tumours was followed by c-MYC immunohistochemistry and dual-colour MYC and centromere 8 (CEN8) chromogenic in situ hybridisation on formalin-fixed paraffin-embedded sections. Clinicopathological data were collected, interpreted and analysed.
HIV seropositive patients comprised 81% (93/115), mean age 42 (SD 10.8) years, with 55% males, HIV negative patients comprised 19% (22/115), mean age 57 (SD 16.7) years (p = 0.001), with 59% males and the HIV status was unknown for 8 patients. The median CD4 count was 162 (IQR 215) cells/mm, 33% of patients presented with CD4 counts <100 cells/mm and the median viral load was 217 (IQR 182 981) copies/mL. There was advanced stage at presentation (i.e., III-IV, 87%), with Ki-67 proliferation indices ≥90% in 85%- and c-MYC expression (i.e., ≥40%) in 58% of tumours. Double expression of c-MYC and BCL2 was associated with a non-germinal center immunophenotype (p < 0.01). Low-level increase of MYC gene copy numbers and MYC rearrangements occurred in 57% and 12%, respectively. C8 polysomy, MYC gene clusters and concurrent MYC rearrangement/increased MYC gene copies were also detected. Inferior median overall survival (OS) occurred when the CD4 counts were <100 cells/mm (149 days 95% CI 44-254, p 0,04) and when IPI scores were 3-5 [155 days (95% CI 37-273), p = 0.01]. Concomitant infections negatively impacted the survival outcome, multivariate regression analysis (HR 4.01, 95% CI 1.86-12.20, p = 0.02).
c-MYC protein expression, low-level increase in MYC gene copy numbers, rearrangement, C8 polysomy, MYC gene clusters and concurrent MYC rearrangement/low-level gains are present in HIV+ DLBCL. CD4 counts < 100 cells/mm, IPI scores 3-5 and concomitant infections negatively impact the survival outcome.
由于南部非洲地区人类免疫缺陷病毒（HIV）感染的高血清流行率，弥漫性大 B 细胞淋巴瘤（DLBCL）占南非非霍奇金淋巴瘤的 43%。我们探讨了一系列临床病理因素，包括 MYC 基因拷贝数，对 HIV 相关 DLBCL 的预后影响。
对 123 例肿瘤进行回顾性纳入，随后对福尔马林固定石蜡包埋切片进行 c-MYC 免疫组织化学和双色 MYC 和着丝粒 8（CEN8）显色原位杂交。收集、解释和分析临床病理数据。
HIV 阳性患者占 81%（93/115），平均年龄 42（SD 10.8）岁，男性占 55%，HIV 阴性患者占 19%（22/115），平均年龄 57（SD 16.7）岁（p = 0.001），男性占 59%，8 例患者的 HIV 状态未知。中位 CD4 计数为 162（IQR 215）个细胞/mm，33%的患者 CD4 计数<100 个细胞/mm，中位病毒载量为 217（IQR 182981）拷贝/ml。有晚期疾病（即 III-IV 期，87%），Ki-67 增殖指数≥90%的占 85%，肿瘤中 c-MYC 表达（即≥40%）占 58%。c-MYC 和 BCL2 的双重表达与非生发中心免疫表型相关（p<0.01）。MYC 基因拷贝数的低水平增加和 MYC 重排在分别为 57%和 12%。还检测到 C8 多倍体、MYC 基因簇和同时发生的 MYC 重排/增加的 MYC 基因拷贝数。当 CD4 计数<100 个细胞/mm（149 天 95%CI 44-254，p 0.04）和 IPI 评分 3-5 时[155 天（95%CI 37-273），p=0.01]，中位总生存期（OS）降低。同时发生的感染对生存结果有负面影响，多变量回归分析（HR 4.01，95%CI 1.86-12.20，p=0.02）。
在 HIV+ DLBCL 中存在 c-MYC 蛋白表达、MYC 基因拷贝数的低水平增加、重排、C8 多倍体、MYC 基因簇和同时发生的 MYC 重排/低水平增益。CD4 计数<100 个细胞/mm、IPI 评分 3-5 和同时发生的感染对生存结果有负面影响。
