Guenova M, Rassidakis G Z, Gorgoulis V G, Angelopoulou M K, Siakantaris M R, Kanavaros P, Pangalis G A, Kittas C
Department of Morphology, National Center of Hematology and Transfusiology, Sofia, Bulgaria.
Mod Pathol. 1999 Nov;12(11):1062-71.
In order to understand better the possible role of cell-cycle regulating molecules in the pathogenesis of Hodgkin's disease (HD), the immunohistochemical distribution pattern of p16INK4A was investigated and compared with pRb, p53, and MDM2 protein status in 44 HD cases. Our findings were correlated to the presence of Epstein-Barr virus as detected by RNA in situ hybridization and clinicopathological parameters. p16INK4A protein immunoreactivity was found in all 44 cases with a proportion of Hodgkin-Reed-Sternberg (HRS) cells ranging from 30 to 90%. In 93% of the cases studied, pRb was detected in HRS, whereas all cases showed overexpression of p53. Almost all specimens (98%) were MDM2-positive as evaluated by 1B10 and/or IF2 monoclonal antibodies. EBER 1/2-transcripts were detected in 31.8% (14 of 44) of the examined samples. A significant correlation was observed between immunoreactivity of p16INK4A and MDM2 and the number of HRS cells (P = .0012 and P = .018, respectively). In a subgroup of cases, with p16INK4A expression in more than 50% of HRS cells, the percentage of pRb-positive neoplastic cells was inversely related to that of p16-positive ones (P = .007). No clinicopathological parameters or clinical prognostic indicators, including duration of response to therapy, were statistically related to the expression levels of any of the four proteins investigated or the presence of Epstein-Barr virus. Our findings suggest that p16 and pRb are regularly expressed and that their pathway in cell-cycle machinery seems to be intact in HD. However, further investigation is needed to shed light on the involvement of cell-cycle molecules in Hodgkin's lymphomagenesis and longer patient follow-up is required for conclusive prognostic correlation.
为了更好地理解细胞周期调节分子在霍奇金淋巴瘤（HD）发病机制中的可能作用，我们研究了44例HD病例中p16INK4A的免疫组化分布模式，并将其与pRb、p53和MDM2蛋白状态进行了比较。我们的研究结果与通过RNA原位杂交检测到的爱泼斯坦 - 巴尔病毒的存在以及临床病理参数相关。在所有44例病例中均发现了p16INK4A蛋白免疫反应性，霍奇金 - 里德 - 斯腾伯格（HRS）细胞的比例为30%至90%。在93%的研究病例中，HRS细胞中检测到了pRb，而所有病例均显示p53过表达。通过1B10和/或IF2单克隆抗体评估，几乎所有标本（98%）均为MDM2阳性。在31.8%（44例中的14例）的检测样本中检测到了EBER 1/2转录本。观察到p16INK4A和MDM2的免疫反应性与HRS细胞数量之间存在显著相关性（分别为P = 0.0012和P = 0.018）。在一个亚组病例中，p16INK4A在超过50%的HRS细胞中表达，pRb阳性肿瘤细胞的百分比与p16阳性细胞的百分比呈负相关（P = 0.007）。包括治疗反应持续时间在内的任何临床病理参数或临床预后指标与所研究的四种蛋白质的表达水平或爱泼斯坦 - 巴尔病毒的存在均无统计学相关性。我们的研究结果表明，p16和pRb正常表达，并且它们在细胞周期机制中的通路在HD中似乎是完整的。然而，需要进一步研究以阐明细胞周期分子在霍奇金淋巴瘤发生中的作用，并且需要对患者进行更长时间的随访以进行确定性的预后相关性研究。
