Objective: To investigate the expression of CD137 in HRS cells of classical Hodgkin Lymphoma (cHL), and its application in the pathological differential diagnosis.
Methods: 54 cases of cHL with "HRS" cells, and 55 cases of non-cHL with "HRS-like" cells as control group were collected. "HRS" cells and "HRS-like" cells rich areas in slides were selected from relevant groups to produce two tissue microarrays. This study focused solely on "HRS" cells and "HRS-like" cells, immunohistochemical staining for antibodies including CD30, CD15, CD20, CD3, and PAX5 were performed on CHL cases, CD137 (clone BBK-2) immunostaining and EBER in situ hybridization were detected in both groups.
Results: All cHL cases aged 22.0-68.0 (median 45.5) years with the male to female ratio as about 1.7∶1 primarily involved lymph nodes; while in the control group, 54 cases aged 12.0-81.0 (median 50.0) years with male∶female=1.9∶1 primarily located in nodes with only 1 case in skin. In the cHL group, CD30, CD15, CD20 and CD3 were positive in 100.0%, 70.4%, 18.5% and 0 cases in order, and PAX5 showed weak to moderate positive in 70.4% cases; the positive rate of EBER was 25.9% in cHL group, and 21.8% in the control group; The CD137 positive rates were 57.4% in cHL and 14.5% in the control groups with a significant difference (P<0.001). There were no significant differences when CD137 expressions were further compared according to the differences in age [elder group (aged 60) /non elderly group], gender (male/female), EBV infection (yes/no), histological subtype and the expression of those major diagnostic markers (positive/negative) in either cHL or control groups (all P valued>0.05). The positive rates of CD137 expression in cHL were significantly different when sub-grouped according to accession year before or after 2013 (39.4% vs 85.7%, P=0.001); However, no difference was seen in the control group (12.5% vs 16.1% , P=0.705). For those cases after 2013, the CD137 positive ratio of cHL group was more significantly different with the control one (85.7% vs 16.1%, P<0.001).
Conclusion: Frequent expression of CD137 in "HRS" cells of cHL cases from Northern China could be detected by IHC method, while the CD137 expression was much lower in "HRS-like" cells of the control group. The positive rate of CD137 expression by immunohistochemical staining significantly increased in this cohort stored less than 3 years, which might be more reliable. CD137 might be potentially applied on pathological differential diagnosis of cHL.
目的: 明确CD137在北方地区经典型霍奇金淋巴瘤（cHL）中的表达，探讨其作为cHL辅助病理鉴别诊断新指标的可能应用价值。
方法: 收集54例cHL患者资料，以55例伴有“HRS样细胞”的非cHL患者为对照。在病理组织标本中选取“HRS细胞”或“HRS样细胞”丰富的区域制作组织芯片；以“HRS细胞”或“HRS样细胞”为观察对象，cHL组应用CD30、CD15、CD20、PAX5、CD3免疫组织化学染色；同时对两组患者标本进行CD137（BBK-2）抗体免疫组织化学染色及采用EBV编码的小RNA（EBER）原位杂交法检测EBV感染状态。
结果: 54例cHL患者均为淋巴结内原发，中位年龄45.5（22.0~68.0）岁；男女比例1.7∶1；对照组患者结内54例，结外（皮肤）1例，中位年龄50.0（12.0~81.0）岁；男女比例1.9∶1。54例cHL患者均表达CD30，HRS细胞主要诊断相关免疫标志物CD30、CD15、CD20、CD3阳性表达率依次为100.0%、70.4%、18.5％和0，可见PAX5弱至中等强度表达，阳性率70.4%；EBV感染阳性率25.9%（对照组阳性率21.8%）。cHL组CD137阳性率57.4%，对照组阳性率14.5%，差异有统计学意义（P<0.001）。将cHL组及对照组按照患者年龄（≥60/<60岁）、性别、有无EBV感染、组织学亚型以及主要诊断相关标志物的表达与否进行分组，CD137阳性率差异均无统计学意义（P值均> 0.05）。以2013年为界进行分组，2013年前后两组cHL患者的CD137阳性率差异有统计学意义（39.4%对85.7%，P=0.001），对照组差异无统计学意义（12.5％对16.1%，P=0.705）；2013以后存档的标本中cHL组与对照组患者CD137阳性率差异有统计学意义（85.7％对16.1%，P<0.001）。
结论: 通过研究初步证实北方地区大多数cHL患者的HRS细胞表达CD137，而对照组患者“HRS样细胞”CD137阳性率较低。保存期3年以内较保存期3年以上的cHL患者标本CD137阳性率高，更适于进行CD137免疫组织化学染色检测。CD137有望作为辅助cHL病理鉴别诊断的新指标。