Departments of Pathology, Affiliated Yantai Yuhuangding Hospital, Qingdao University, 20 Yuhuangding East Road, Yantai, 264000, China.
The 2nd Medical College of Binzhou Medical University, 346 Guanhai Road, Yantai, China.
Diagn Pathol. 2024 Nov 21;19(1):149. doi: 10.1186/s13000-024-01577-z.
The positive expression of Cyclin D1 in immunohistochemical (IHC) staining serves as the cornerstone for diagnosing mantle cell lymphoma (MCL). However, existing literature does not conclusively establish whether the expression ratio and staining intensity significantly influence diagnostic outcomes or patient prognosis. In this retrospective study, the correlation between comprehensive Cyclin D1 quantification and the prognosis of MCL patients was studied.
The Cyclin D1 protein level was assessed in 120 formalin-fixed paraffin-embedded samples from MCL patients using the quantitative dot blot (QDB) analysis technique. R language software was employed for statistical analysis to determine the optimal threshold with statistical significance. Additionally, Kaplan-Meier method was utilized to evaluate the relationship between the absolute level of Cyclin D1 protein and overall survival (OS) of patients. Furthermore, the Chi-square test was applied to analyze the causes of single and multiple fractures, with a significance level of p < 0.05. Finally, the Log-rank test was used to compare two survival curves, where a significance level of p < 0.05 was considered statistically significant.
At the optimized cutoff of 0.46 nmol/g, univariate analysis revealed a positive correlation between Cyclin D1 protein level and patient survival (OS). Specifically, in the subgroup with complete quantification of Cyclin D1 higher than the cutoff, the 5-year OS was 18%, whereas in the subgroup with complete quantification of Cyclin D1 lower than the cutoff, the 5-year OS was 4.8% (Log-rank test, P = 0.017). This indicates that patients with Cyclin D1 levels above the cutoff had significantly better overall survival compared to those below the cutoff. Additionally, in the Pearson distribution test, Ki-67 emerged as an independent prognostic factor for the complete quantification of Cyclin D1. Notably, Cyclin D1 complete quantification results remained unaffected by factors such as gender, age, LDH (Lactate Dehydrogenase) level, Ann Arbor stage(AAS), Ki-67, IPI(International prognostic index), MIPI(Mantle International prognostic index), and MIPI-c (MIPI Combined with Ki-67 Proliferation Index Chi-square test, p > 0.05).
Comprehensive Cyclin D1 quantification, especially above a threshold, significantly correlates with better overall survival in MCL. This highlights its prognostic importance in MCL management. Full quantification of CyclinD1 aids MCL prognosis, while QDB technology for biomarker quantification supports precise clinical prognostic stratification.
Cyclin D1 在免疫组织化学（IHC）染色中的阳性表达是诊断套细胞淋巴瘤（MCL）的基石。然而，现有文献并未明确表达比值和染色强度是否显著影响诊断结果或患者预后。在这项回顾性研究中，研究了全面的 Cyclin D1 定量与 MCL 患者预后之间的相关性。
使用定量斑点印迹（QDB）分析技术评估了 120 例 MCL 患者福尔马林固定石蜡包埋样本中的 Cyclin D1 蛋白水平。使用 R 语言软件进行统计分析，以确定具有统计学意义的最佳阈值。此外，采用 Kaplan-Meier 方法评估 Cyclin D1 蛋白绝对水平与患者总生存（OS）之间的关系。此外，采用卡方检验分析单发和多发骨折的原因，显著性水平 p<0.05。最后，采用 Log-rank 检验比较两条生存曲线，显著性水平 p<0.05 认为具有统计学意义。
在优化的 0.46 nmol/g 截断值处，单因素分析显示 Cyclin D1 蛋白水平与患者生存（OS）呈正相关。具体而言，在 Cyclin D1 完全定量高于截断值的亚组中，5 年 OS 为 18%，而在 Cyclin D1 完全定量低于截断值的亚组中，5 年 OS 为 4.8%（Log-rank 检验，P=0.017）。这表明 Cyclin D1 水平高于截断值的患者总生存明显优于低于截断值的患者。此外，在 Pearson 分布检验中，Ki-67 是 Cyclin D1 完全定量的独立预后因素。值得注意的是，Cyclin D1 完全定量结果不受性别、年龄、乳酸脱氢酶（LDH）水平、Ann Arbor 分期（AAS）、Ki-67、国际预后指数（IPI）、Mantle 国际预后指数（MIPI）和 MIPI-c（MIPI 与 Ki-67 增殖指数的联合卡方检验，p>0.05）等因素的影响。
全面的 Cyclin D1 定量，尤其是高于阈值，与 MCL 患者的总体生存显著相关。这突出了其在 MCL 管理中的预后重要性。CyclinD1 的完全定量有助于 MCL 预后，而 QDB 技术用于生物标志物定量支持精确的临床预后分层。
