Clinical significance of Cyclin D1 by complete quantification detection in mantle cell lymphoma: positive indicator in prognosis

Abstract Objectives 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...

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Main Authors: Yan Yang, Liling Song, Ying Yin, Yuan Gao, Yunjun Wang, Shishou Wu, Jun Wang, Yu Pan, Xiaolong Sui, Lei Jiang, Yunyun Zhang, Guohua Yu
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Diagnostic Pathology
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Online Access:https://doi.org/10.1186/s13000-024-01577-z
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author Yan Yang
Liling Song
Ying Yin
Yuan Gao
Yunjun Wang
Shishou Wu
Jun Wang
Yu Pan
Xiaolong Sui
Lei Jiang
Yunyun Zhang
Guohua Yu
author_facet Yan Yang
Liling Song
Ying Yin
Yuan Gao
Yunjun Wang
Shishou Wu
Jun Wang
Yu Pan
Xiaolong Sui
Lei Jiang
Yunyun Zhang
Guohua Yu
author_sort Yan Yang
collection DOAJ
description Abstract Objectives 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. Methods 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. Results 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). Conclusions 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.
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spelling doaj-art-04e97bd44cbb4685a5a0e9a078853ff62025-08-20T02:22:32ZengBMCDiagnostic Pathology1746-15962024-11-011911910.1186/s13000-024-01577-zClinical significance of Cyclin D1 by complete quantification detection in mantle cell lymphoma: positive indicator in prognosisYan Yang0Liling Song1Ying Yin2Yuan Gao3Yunjun Wang4Shishou Wu5Jun Wang6Yu Pan7Xiaolong Sui8Lei Jiang9Yunyun Zhang10Guohua Yu11Departments of Pathology, Affiliated Yantai Yuhuangding Hospital, Qingdao UniversityThe 2nd Medical College of Binzhou Medical UniversityDepartments of Pathology, Affiliated Yantai Yuhuangding Hospital, Qingdao UniversityDepartments of Pathology, Affiliated Yantai Yuhuangding Hospital, Qingdao UniversityDepartments of Pathology, Affiliated Yantai Yuhuangding Hospital, Qingdao UniversityDepartments of Pathology, Affiliated Yantai Yuhuangding Hospital, Qingdao UniversityDepartments of Pathology, Affiliated Yantai Yuhuangding Hospital, Qingdao UniversityDepartments of Pathology, Affiliated Yantai Yuhuangding Hospital, Qingdao UniversityDepartments of Pathology, Affiliated Yantai Yuhuangding Hospital, Qingdao UniversityDepartments of Pathology, Affiliated Yantai Yuhuangding Hospital, Qingdao UniversityYantai Quanticision DiagnosticsDepartments of Pathology, Affiliated Yantai Yuhuangding Hospital, Qingdao UniversityAbstract Objectives 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. Methods 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. Results 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). Conclusions 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.https://doi.org/10.1186/s13000-024-01577-zCyclin D1QDBMCLProtein quantitationPrognosis
spellingShingle Yan Yang
Liling Song
Ying Yin
Yuan Gao
Yunjun Wang
Shishou Wu
Jun Wang
Yu Pan
Xiaolong Sui
Lei Jiang
Yunyun Zhang
Guohua Yu
Clinical significance of Cyclin D1 by complete quantification detection in mantle cell lymphoma: positive indicator in prognosis
Diagnostic Pathology
Cyclin D1
QDB
MCL
Protein quantitation
Prognosis
title Clinical significance of Cyclin D1 by complete quantification detection in mantle cell lymphoma: positive indicator in prognosis
title_full Clinical significance of Cyclin D1 by complete quantification detection in mantle cell lymphoma: positive indicator in prognosis
title_fullStr Clinical significance of Cyclin D1 by complete quantification detection in mantle cell lymphoma: positive indicator in prognosis
title_full_unstemmed Clinical significance of Cyclin D1 by complete quantification detection in mantle cell lymphoma: positive indicator in prognosis
title_short Clinical significance of Cyclin D1 by complete quantification detection in mantle cell lymphoma: positive indicator in prognosis
title_sort clinical significance of cyclin d1 by complete quantification detection in mantle cell lymphoma positive indicator in prognosis
topic Cyclin D1
QDB
MCL
Protein quantitation
Prognosis
url https://doi.org/10.1186/s13000-024-01577-z
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