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Clinicopathological Significance of DNA Replication Licensing Factors in Head and Neck Diffuse Large B-cell Lymphoma

DNA Replication Licensing Factors in Diffuse Large B-Cell Lymphoma
Published:November 01, 2021DOI:https://doi.org/10.1016/j.oooo.2021.10.018

      Abstract

      Objectives

      Diffuse large B-cell lymphoma (DLBCL) harbors defects in the proliferation pathway. We performed multiparameter analysis of proteins expressed during different cell-cycle phases and correlated them with clinical parameters of head and neck DLBCLs.

      Study Design

      Thirty-nine DLBCLs were staged and immunohistochemically stained with MCM2, ki67 and geminin. Receiver-operating characteristic curve and its area-under-curve (AUC) were calculated and sensitivity vs specificity curve analysis was performed.

      Results

      The highest labeling-index was in MCM2 followed by ki67 and geminin (P<0.001). All pairs showed significant differences (P<0.001). Best cut-off points to differentiate limited from advanced disease were 68% and 45% for MCM2 and ki67, respectively. There was no acceptable cut-off for geminin (AUC=0.667, P=0.134). MCM2/ki67 (P=0.293) and geminin/ki67 (P=0.233) ratios did not differ between the stages. Median(IQR) of geminin/ki67 ratio was 0.57(0.68), translating to a reduced-G1.

      Conclusions

      We suggest a role for cell-cycle-related proteins in the biology and behavior of DLBCLs. MCM2 and ki67 cut-offs can be a potential option to differentiate limited from advanced disease, where imaging and laboratory techniques are unavailable. G1 decrease and the significantly higher MCM2 expression compared to ki67, indicate replication disturbances, making factors involved in the G1 phase, targets for treatment.
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