Phospho-histone-H3 immunostaining for pulmonary carcinoids: impact on clinical appraisal, interobserver correlation, and diagnostic processing efficiency

Laflamme, Philippe; Mansoori, Babak Khoshkrood; Sazanova, Olga; Orain, Michèle; Couture, Christian; Simard, Serge; Trahan, Sylvain; Manem, Venkata S. K.; Joubert, Philippe

doi:10.1016/j.humpath.2020.09.009

Cited by 7 publications

(7 citation statements)

References 27 publications

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“…To further distinguish the impact of PPP1R14B on G 2 or M phase of the cell cycle, flow cytometry analysis was performed using the p-H3 S10 antibody to detect mitotic cells. It has been well documented that p-H3 S10 is a specific marker in mitosis and exists only during the late G 2 phase and mitosis ( 31 ). Results showed that the percentage of p-H3 S10-positive cells was obviously increased after PPP1R14B knockdown (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Protein Phosphatase 1 Subunit PPP1R14B Stabilizes STMN1 to Promote Progression and Paclitaxel Resistance in Triple-Negative Breast Cancer

et al. 2022

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Triple-negative breast cancer (TNBC) represents the most lethal subtype of breast cancer due to its aggressive clinical features and the lack of effective therapeutic targets. To identify novel approaches for targeting TNBC, we examined the role of protein phosphatases in TNBC progression and chemoresistance. Protein phosphatase 1 regulatory subunit 14B (PPP1R14B), a poorly defined member of the protein phosphatase 1 regulatory subunits, was aberrantly upregulated in TNBC tissues and predicted poor prognosis. PPP1R14B was degraded mainly through the ubiquitin-proteasome pathway. RPS27A recruited deubiquitinase USP9X to deubiquitinate and stabilize PPP1R14B, resulting in overexpression of PPP1R14B in TNBC tissues. Gain- and loss-of-function assays demonstrated that PPP1R14B promoted TNBC cell proliferation, colony formation, migration, invasion, and resistance to paclitaxel in vitro. PPP1R14B also induced xenograft tumor growth, lung metastasis and paclitaxel resistance in vivo. Mechanistic investigations revealed that PPP1R14B maintained phosphorylation and stability of oncoprotein stathmin 1 (STMN1), a microtubule-destabilizing phosphoprotein critically involved in cancer progression and paclitaxel resistance, which was dependent on PP1 catalytic subunits α and γ. Importantly, the tumor suppressive effects of PPP1R14B deficiency could be partially rescued by ectopic expression of wild-type but not phosphorylation-deficient STMN1. Moreover, PPP1R14B increased STMN1-mediated α-tubulin acetylation, microtubule stability, and cell-cycle progression, leading to resistance of TNBC cells to paclitaxel. Collectively, these findings uncover a functional and mechanistic role of PPP1R14B in TNBC progression and paclitaxel resistance, indicating PPP1R14B is a potential therapeutic target for TNBC.

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Section: Resultsmentioning

confidence: 99%

Protein Phosphatase 1 Subunit PPP1R14B Stabilizes STMN1 to Promote Progression and Paclitaxel Resistance in Triple-Negative Breast Cancer

et al. 2022

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“…Hypothetical classification systems were created by replacing the mitotic count criteria with the measured expression of Ki-67 and PHH3, with nine threshold values chosen for each marker to explore the effect of thresholds, which is often debated. 8 , 14 The classification’s relevance was assessed based on the reproducibility of the diagnoses and the prognostic value of the two groups obtained, by majority voting, according to recurrence-free survival (RFS) after surgery, which considers patients who have relapsed or died of the disease or from an unreported cause. To assess whether the new classification systems defining ‘new groups’ had similar or different prognostic values to the official classification, we measured the differences in prognosis between the new groups (Cox model 1); we also compared prognosis between the new ACs and consensus ACs (Cox model 2).…”

Section: Methodsmentioning

confidence: 99%

Assessment of the current and emerging criteria for the histopathological classification of lung neuroendocrine tumours in the lungNENomics project

Mathian,

Drouet,

Sexton-Oates

et al. 2024

ESMO Open

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“…57 Indeed, mitotic figures are unevenly distributed across the tumour tissue, with large random effects, and unfortunately the current guidelines do not suggest any preferential method for mitotic counting. A possible solution for precise mitotic counting is IHC for phosphohistone H3 (PHH3), a marker of mitotic figures, which has been suggested to reduce interobserver variability in many tumour entities, including lung carcinoids, [58][59][60][61][62] but its use in routine grading requires validation.…”

Section: Diagnostic Reproducibilitymentioning

confidence: 99%

Updates on lung neuroendocrine neoplasm classification

Vocino Trucco,

Righi,

Volante

et al. 2023

Histopathology

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Lung neuroendocrine neoplasms (NENs) are a heterogeneous group of pulmonary neoplasms showing different morphological patterns and clinical and biological characteristics. The World Health Organisation (WHO) classification of lung NENs has been recently updated as part of the broader attempt to uniform the classification of NENs. This much‐needed update has come at a time when insights from seminal molecular characterisation studies revolutionised our understanding of the biological and pathological architecture of lung NENs, paving the way for the development of novel diagnostic techniques, prognostic factors and therapeutic approaches. In this challenging and rapidly evolving landscape, the relevance of the 2021 WHO classification has been recently questioned, particularly in terms of its morphology‐orientated approach and its prognostic implications. Here, we provide a state‐of‐the‐art review on the contemporary understanding of pulmonary NEN morphology and the potential contribution of artificial intelligence, the advances in NEN molecular profiling with their impact on the classification system and, finally, the key current and upcoming prognostic factors.

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Phospho-histone-H3 immunostaining for pulmonary carcinoids: impact on clinical appraisal, interobserver correlation, and diagnostic processing efficiency

Cited by 7 publications

References 27 publications

Protein Phosphatase 1 Subunit PPP1R14B Stabilizes STMN1 to Promote Progression and Paclitaxel Resistance in Triple-Negative Breast Cancer

Protein Phosphatase 1 Subunit PPP1R14B Stabilizes STMN1 to Promote Progression and Paclitaxel Resistance in Triple-Negative Breast Cancer

Assessment of the current and emerging criteria for the histopathological classification of lung neuroendocrine tumours in the lungNENomics project

Updates on lung neuroendocrine neoplasm classification

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