The Utility of Phosphohistone H3 (PHH3) in Follicular Lymphoma Grading: A Comparative Study With Ki-67 and H&amp;E Mitotic Count

Khieu, Michelle; Broadwater, Devin R.; Aden, James K; Coviello, Jean M.; Lynch, David T.; Hall, Jordan

doi:10.1093/ajcp/aqz003

Cited by 12 publications

(7 citation statements)

References 21 publications

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“…2 ). In addition, as has been previously described in follicular lymphoma and breast cancer, there was a statistically significant association between MAI and PHH3 ( p < 0.001), expected because the PHH3 antibody is a specific IHC biomarker of MF and because it was used the same quantification criteria, both in the H-E slides for MAI and in those for IHC ( 9 , 18 , 19 , 21 ).…”

Section: Discussionsupporting

confidence: 75%

“…In anaphase, the dephosphorylation process of histone H3 begins, which ends in early telophase ( 9 , 11 , 16 ). The PHH3 antibody is characterized by presenting a clear and well contrasted immunostaining, limited to cells that are in the M phase of the cell cycle, while interphase cells do not express it or do so minimally ( 9 , 11 , 18 ). Although it has been recognized as a prognostic marker in multiple types of cancer, it has been scarcely analyzed in OSCC and, in particular, its relationship with survival rate has not been the subject of research until now ( 16 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

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The value of Phosphohistone H3 as a cell proliferation marker in oral squamous cell carcinoma. A comparative study with Ki-67 and the mitotic activity index

Tancredi-Cueto¹,

Vigil-Bastitta²,

Bologna-Molina³

et al. 2022

Med Oral

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Background The Phosphohistone H3 (PHH3) antibody is recognized as a biomarker of cell proliferation, specific for cells in mitosis, of prognostic value in different malignant neoplasms, however it has been poorly studied in oral squamous cell carcinoma (OSCC). The main objective of this study was to evaluate the immunoexpression of the PHH3 in the OSCC, through the correlation with the immunoexpression of Ki-67, the mitotic activity index (MAI), histological grading, clinical-morphological parameters and the rate of survival. Material and Methods The study sample consisted of 62 cases of OSCC diagnosed in the Pathological Anatomy Laboratory of the Faculty of Dentistry, University of the Republic (Uruguay). In each of them, an immunohistochemical technique was performed for Ki-67 and PHH3 (serine 10) antibodies. Image J software was used for the MAI and biomarker quantification, defining the percentage of positivity and mitotic Figures per 1000 tumor cells. Results a significant association was obtained between the expression of PHH3 ( p 0.016) and MAI ( p 0.031) with survival time. However, no similar relationship was found with Ki-67 ( p 0.295). Although it was confirmed a statistical association between histological grade and Ki-67 immunoexpression ( p 0.004), PHH3 did not show a similar relationship ( p 0.564). Conclusions It was confirmed the role of the PHH3 antibody as a biomarker of mitotic Figures in OSCC and as a potential marker of cell proliferation. It is noteworthy that this is one of the first works that evaluates a possible relationship between the expression of this antibody and survival in OSCC. Key words: Oral squamous cell carcinoma, phosphohistone H3, Ki-67, cell proliferation.

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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

The value of Phosphohistone H3 as a cell proliferation marker in oral squamous cell carcinoma. A comparative study with Ki-67 and the mitotic activity index

Tancredi-Cueto¹,

Vigil-Bastitta²,

Bologna-Molina³

et al. 2022

Med Oral

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“…IHC analysis of tumor sections (Fig. 4C ) confirmed complete macrophage depletion (F4/80+), and a significant reduction of mitotic index indicated by a complete reduction of pH3 + cells, a hallmark of active cell proliferation [ 34 ]. In addition, clodronate-treated tumors appeared scarcely vascularized (Fig.…”

Section: Resultsmentioning

confidence: 99%

The receptor of the colony-stimulating factor-1 (CSF-1R) is a novel prognostic factor and therapeutic target in follicular lymphoma

et al. 2021

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Microenvironment contributes to follicular lymphoma (FL) pathogenesis and impacts survival with macrophages playing a controversial role. In the present study, using FL primary samples and HK follicular dendritic cells (FDC) to mimic the germinal center, together with mouse models, we have analyzed the three-way crosstalk of FL-FDC-macrophages and derived therapeutic opportunities. Ex vivo primary FL-FDC co-cultures (n = 19) and in vivo mouse co-xenografts demonstrated that FL-FDC crosstalk favors tumor growth and, via the secretion of CCL2 and CSF-1, promotes monocyte recruitment, differentiation, and polarization towards an M2-like protumoral phenotype. Moreover, FL-M2 co-cultures displayed enhanced angiogenesis, dissemination, and immunosuppression. Analysis of the CSF-1/CSF-1R pathway uncovered that CSF-1 was significantly higher in serum from grade 3A FL patients, and that high CSF-1R expression in FL biopsies correlated with grade 3A, reduced overall survival and risk of transformation. Furthermore, CSF-1R inhibition with pexidartinib (PLX3397) preferentially affected M2-macrophage viability and polarization program disrupting FL-M2 positive crosstalk. In vivo CSF1-R inhibition caused M2 reduction and repolarization towards M1 macrophages and antitumor effect cooperating with anti-CD20 rituximab. In summary, these results support the role of macrophages in FL pathogenesis and indicate that CSF-1R may be a relevant prognostic factor and a novel therapeutic target cooperating with anti-CD20 immunotherapy.

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“…Phosphorylation of H3 at serine 10 (phospho-H3) results in immediate condensation of the chromatin in the late G2 phase of the cell cycle, and thus, is a marker present in dividing cells [ 207 ]. Indeed, mitotic activity determined by phospho-H3 counting has been experimentally and clinically used to measure cell proliferation in different types of cancer, including lymphoma [ 207 , 208 , 209 , 210 ]. Thus, the discovery of compounds that target histone phosphorylation is an interesting approach for the treatment of oncological patients.…”

Section: Targeting Histone Methylation and Some Other Ptmsmentioning

confidence: 99%

Histone Modifications and Their Targeting in Lymphoid Malignancies

Fernández-Serrano

Winkler

Santos

et al. 2021

IJMS

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In a wide range of lymphoid neoplasms, the process of malignant transformation is associated with somatic mutations in B cells that affect the epigenetic machinery. Consequential alterations in histone modifications contribute to disease-specific changes in the transcriptional program. Affected genes commonly play important roles in cell cycle regulation, apoptosis-inducing signal transduction, and DNA damage response, thus facilitating the emergence of malignant traits that impair immune surveillance and favor the emergence of different B-cell lymphoma subtypes. In the last two decades, the field has made a major effort to develop therapies that target these epigenetic alterations. In this review, we discuss which epigenetic alterations occur in B-cell non-Hodgkin lymphoma. Furthermore, we aim to present in a close to comprehensive manner the current state-of-the-art in the preclinical and clinical development of epigenetic drugs. We focus on therapeutic strategies interfering with histone methylation and acetylation as these are most advanced in being deployed from the bench-to-bedside and have the greatest potential to improve the prognosis of lymphoma patients.

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The Utility of Phosphohistone H3 (PHH3) in Follicular Lymphoma Grading: A Comparative Study With Ki-67 and H&E Mitotic Count

Cited by 12 publications

References 21 publications

The value of Phosphohistone H3 as a cell proliferation marker in oral squamous cell carcinoma. A comparative study with Ki-67 and the mitotic activity index

The value of Phosphohistone H3 as a cell proliferation marker in oral squamous cell carcinoma. A comparative study with Ki-67 and the mitotic activity index

The receptor of the colony-stimulating factor-1 (CSF-1R) is a novel prognostic factor and therapeutic target in follicular lymphoma

Histone Modifications and Their Targeting in Lymphoid Malignancies

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