High Phosphohistone H3 Expression Correlates with Adverse Clinical, Biological, and Pathological Factors in Neuroblastomas

Ramani, Pramila; Taylor, Scott; Miller, Elizabeth E.; Sowa-Avugrah, Emile; May, Margaret T

doi:10.1369/0022155415576966

Cited by 9 publications

(11 citation statements)

References 35 publications

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“…PHH3, which is expressed during late G2 and M, is a specific immunohistochemical indicator of proliferating cells in FFPE sections. Furthermore, immunohistochemical detection of PHH3 is useful for grading, prognostication, assessment of the risk of recurrence, and as an indicator of the response to treatment of patients with meningioma, esophageal squamous cell carcinoma, cutaneous melanoma, prostate adenocarcinoma, or neuroblastoma 24,26–29 . Moreover, PHH3 immunohistochemistry improves the reproducibility of assessing the risk of recurrence of gastrointestinal stromal tumors 30 .…”

Section: Discussionmentioning

confidence: 99%

High phospho‐histone H3 expression uniquely predicts favorable survival among four markers of cellular proliferation in colorectal cancer

Koshino

Inoue

Sugimura-Nagata

et al. 2021

Pathology International

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Colorectal cancer (CRC) is one of the most frequent gastrointestinal cancers worldwide, with high morbidity and mortality rates. Despite numerous attempts to identify prognostic markers for the CRC patients, the significance of the association of cellular proliferation markers with survival is controversial. Here we used immunohistochemistry to detect four markers of cellular proliferation expressed in primary CRC tissue specimens (n = 269) to assess their potential to serve as prognostic factors. CRC cells variably expressed phospho-histone H3 (PHH3) (range, 0-76 per high-powered field (HPF); median, 7 per HPF), cyclin A (CCNA) (range, 11.3-73.7%; median, 32%), geminin (GMNN) (range, 7.8-82.0%; median, 37.1%), and marker of proliferation Ki-67 (MKI67) (range, 4.9-96.6%; median, 49.6%). Among them, patients with PHH3-high (≥7 per HPF) tumors uniquely experienced significantly longer 5-year survival than those with PHH3-low (≤6 per HPF) (81.8% vs. 65.5%; P = 0.0047). Multivariable Cox hazards regression analysis identified PHH3-high (hazard ratio, 0.54; 95% confidence interval, 0.31-0.92; P = 0.025) as potential favorable factors. PHH3 levels inversely associated with pT stage (P < 0.0001) and were significantly and inversely associated with tumor diameter (ρ = −0.314, P < 0.0001). These findings support the use of PHH3 immunohistochemistry for predicting the prognoses of patients with CRC.

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Section: Discussionmentioning

confidence: 99%

High phospho‐histone H3 expression uniquely predicts favorable survival among four markers of cellular proliferation in colorectal cancer

Koshino

Inoue

Sugimura-Nagata

et al. 2021

Pathology International

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“…The main characteristics of the 19 articles were extracted and are summarized in Table 1 . The patients were from People’s Republic of China, 8 , 13 , 14 Korea, 15 Norway, 10 , 16 – 18 India, 19 Germany, 9 , 20 the United Kingdom, 21 , 22 the United States of America, 11 , 23 New Zealand, 24 Sweden, 25 Australia, 26 and Italy. 27 The types of carcinoma included glioma, neuroblastoma, gastric cancer, gastrointestinal stromal tumor, Merkel cell carcinoma, cutaneous melanoma, uterine smooth muscle tumor, endometrial cancer, adrenocortical carcinoma, prostate cancer, and breast cancer.…”

Section: Resultsmentioning

confidence: 99%

Pooling analysis on prognostic value of PHH3 expression in cancer patients

Hao¹,

Dai²,

Deng³

et al. 2018

CMAR

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BackgroundVarious studies have evaluated the significance of phosphohistone-H3 (PHH3) expression in cancer patients, but controversy over its reliability remains. We conducted a meta-analysis to summarize the prognostic relevance of PHH3 expression in cancer patients.Patients and methodsNineteen studies, including 4803 patients, were identified by searching PubMed, Web of Science, Embase, and Cochrane Library. The correlation of PHH3 expression level with overall survival (OS), disease-free survival, and recurrence-free survival was analyzed.ResultsOverall, the results suggest that high expression of PHH3 can predict a poor OS (HR=2.66, 95% CI=1.74–4.08, P<0.001), disease-free survival (HR=3.40, 95% CI=1.47–7.87, P=0.004), and recurrence-free survival (HR=2.80, 95% CI=1.61–4.85, P<0.001) in cancer patients. The subgroup analysis showed that highly expressed PHH3 was significantly related to breast cancer (HR=5.66, 95% CI=2.72–11.78, P<0.001) and urogenital tumors (HR=3.01, 95% CI=1.78–5.09, P<0.001). Furthermore, no significant difference was found between Asian (HR=1.98, 95% CI=1.08–3.63, P=0.026) and Caucasian populations (HR=3.01, 95% CI=1.87–4.85, P<0.001) regarding OS and PHH3 expression.ConclusionThis meta-analysis indicates that high expression of PHH3 may serve as a biomarker for poor prognosis in patients with cancer.

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“…Histone H3 has a crucial role in chromatin compaction and chromosome formation [ 206 ]. 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 ].…”

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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High Phosphohistone H3 Expression Correlates with Adverse Clinical, Biological, and Pathological Factors in Neuroblastomas

Cited by 9 publications

References 35 publications

High phospho‐histone H3 expression uniquely predicts favorable survival among four markers of cellular proliferation in colorectal cancer

High phospho‐histone H3 expression uniquely predicts favorable survival among four markers of cellular proliferation in colorectal cancer

Pooling analysis on prognostic value of PHH3 expression in cancer patients

Histone Modifications and Their Targeting in Lymphoid Malignancies

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