Nuclear pseudoinclusions in melanoma cells: prognostic fact or artifact? The possible role of Golgi phosphoprotein 3 overexpression in nuclear pseudoinclusions generation

Donizy, Piotr; Kaczorowski, Maciej; Biecek, Przemysław; Hałoń, Agnieszka; Matkowski, Rafał

doi:10.1111/pin.12629

Cited by 3 publications

(3 citation statements)

References 21 publications

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“…In addition, granules with dense cores have been identified in INCIs of PTC 5 . INCIs are also found in the tumor cells of meningioma, 6 pulmonary adenocarcinoma, 7,8 melanocytic tumors, 9–12 and others 13–21 . Although INCIs appear separated from cytoplasm by nuclear compartments and membranes in conventional histology and cytology, an invisible connection to the cytoplasm may be present in these tumors.…”

Section: Introductionmentioning

confidence: 99%

Three‐dimensional structural analysis of papillary thyroid carcinoma nuclei with serial block‐face scanning electron microscopy (SBF‐SEM)

Inoue

Ohno

Oishi

et al. 2023

Pathology International

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Nuclear morphology of carcinoma cells is critical for the pathological diagnosis of papillary thyroid carcinoma (PTC). However, three‐dimensional architecture of PTC nuclei is still elusive. In this study, we analyzed the three‐dimensional ultrastructure of PTC nuclei using serial block‐face scanning electron microscopy which takes advantage of the high‐throughput acquisition of serial electron microscopic images and three‐dimensional reconstruction of subcellular structures. En bloc‐stained and resin‐embedded specimens were prepared from surgically removed PTCs and normal thyroid tissues. We acquired two‐dimensional images from serial block‐face scanning electron microscopy and reconstructed three‐dimensional nuclear structures. Quantitative comparisons showed that the nuclei of carcinoma cells were larger and more complex than those of normal follicular cells. The three‐dimensional reconstruction of carcinoma nuclei divided intranuclear cytoplasmic inclusions into “open intranuclear cytoplasmic inclusions” connecting to cytoplasm outside the nucleus and “closed intranuclear cytoplasmic inclusions” without that connection. Cytoplasm with abundant organelles was observed in open inclusions, but closed inclusions contained fewer organelles with or without degeneration. Granules with a dense core were only observed in closed inclusions. Our observations suggested that open inclusions originate from nuclear invaginations, and disconnection from cytoplasm leads to closed inclusions.

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Section: Introductionmentioning

confidence: 99%

Three‐dimensional structural analysis of papillary thyroid carcinoma nuclei with serial block‐face scanning electron microscopy (SBF‐SEM)

Inoue

Ohno

Oishi

et al. 2023

Pathology International

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“…Proteins for clinical pathology of melanoma are related to epithelial–mesenchymal transition (SPARC and N-cadherin), cell adhesion and migration (ALCAM and ADAM-10), regulation of mitosis (PLK1), cell survival (FOXP1), and the function of the Golgi apparatus (GOLPH3 and GP73) [ 12 ]. A single gene mutation in the hair color gene STX17G causes an unbalanced behavior of melanocytes, leading to gray tendencies and the development of vitiligo and melanoma.…”

Section: Introductionmentioning

confidence: 99%

Differential Gene Expression and Methylation Analysis of Melanoma in TCGA Database to Further Study the Expression Pattern of KYNU in Melanoma

Wang

Huang

et al. 2022

JPM

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Background: The aim of this study was to analyze and compare melanoma gene expression profiles in TCGA database through the application of different genes to explore the pathogenesis of melanoma. Furthermore, we confirmed the extent of the role of KYNU in melanoma and whether it can be a potential target for the diagnosis and treatment of melanoma. Methods: The gene expression profiles of melanoma samples were downloaded from TCGA database, and matrix files were synthesized to screen differential genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis and GCDA broad institute were used to analyze common gene locus mutations and expression changes in melanoma, as well as methylation. In addition, the expression patterns of KYNU in melanoma were quantified by immunohistochemistry, Western blotting, qRT-PCR, software such as GEO DataSets and the Human Protein Atlas, and meta-analysis of skin diseases. KYNU was overexpressed in keratinocytes (HaCaT and HEKα) and melanoma cells (A375 and H1205-lu). CFDA-SE, Annexin V–PI double staining, and PI single staining were used to investigate the mechanism of KYNU in melanoma and its effects on melanoma proliferation, apoptosis, invasion, and migration. Results: The main signaling pathways involved in melanoma were EGF/EGFR–RAS–BRAF–MEK–ERK–CyclinD1/CDK4, Ras–PI3K–PTEN–PKB/AKT, and p14/p16 (CDKN2A)–MDM2–p53–p21–cyclinD1/CDK4/6–Rb/E2F. Moreover, MITF, KIT, CDH1. NRAS, AKT1, EGFR, TP53, KIT, and CDK4 were elevated in melanoma, whereas PTEN, cAMP, and BCL2 were reduced in melanoma. The copy number of tumor-promoting genes increased, while the copy number of tumor suppressor genes decreased. Changes in the copy number of the above tumor genes enriched in chromosomes were found through SNP gene mutations. The genes whose expression was negatively regulated by DNA methylation in melanoma included KRT18, CDK2, JAK3, BCL2, MITF, MET, CXCL10, EGF, SOX10, SOCS3, and KIT. The mutation rate of KYNU was high according to TCGA database. The KYNU level was decreased in melanoma. Overexpression of KYNU can promote changes in apoptotic BCL-2, metabolic KYN, 3-HAA, invasion and migration MMP9, E-cadherin, and other related proteins in melanoma. Fluorescence staining and flow analysis showed that a slower proliferation rate led to a stronger fluorescence intensity. In melanoma tumor cells with a low expression of KYNU, overexpression of KYNU could promote tumor cell apoptosis. IL-10 induced immunoregulatory changes in melanoma. The expression of MMP9 and AMPK decreased in A375, but the change in BCL-2 was not obvious. The expression of BCL-2 decreased significantly in H1205-lu. A375 showed cell-cycle arrest, indicating that IL-10 could slow down the cell cycle of melanoma. Conclusions: These results provide insights into the pathologic mechanisms of melanoma target genes and KYNU as a biomarker and potential therapeutic factor for melanoma.

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“…The presence of NPIs and NGs in the cells of examined tissues may also suggest their malignant character, as is the case in papillary thyroid carcinoma. Yet some authors call into question their significance in the differentiation between malignant and benign lesions (28,29).…”

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confidence: 99%

Nuclear Pseudoinclusions and Intranuclear Grooves Have an Important Impact on the Long-term Survival of Patients With Uveal Melanoma

et al. 2021

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Aim: The evaluation of the prognostic role of nuclear pseudoinclusions (NPIs) and nuclear grooves (NGs) in UM. Patients and Methods: We examined the presence of NPIs and NGs in hematoxylin and eosin-stained tissue sections from 164 removed eyeballs with uveal melanoma (UM) and analyzed statistical relationships with clinical and pathological parameters and the long-term survival rate. Results: We observed NPIs in 38% and NG in 21% of all UM. The presence of NPIs was significantly positively correlated with epithelioid type, marked pleomorphism, and the presence of multinucleated giant cells, macro-nucleoli and multiple nucleoli. Patients with UM with NPIs had a significantly reduced overall survival rate (p<0.0001). The presence of NGs was significantly inversely correlated with marked pleomorphism, and the presence of multinucleated giant cells, macro-nucleoli and multiple nucleoli. Kaplan-Meier analysis demonstrated significantly better overall (p<0.01) and disease-free (p<0.05) survival rates for patients with NGs. Conclusion: The obtained results suggest that the presence of NGs in UM is associated with a better prognosis, as opposed to the presence of NPIs, which means the prognosis is worse.

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Nuclear pseudoinclusions in melanoma cells: prognostic fact or artifact? The possible role of Golgi phosphoprotein 3 overexpression in nuclear pseudoinclusions generation

Cited by 3 publications

References 21 publications

Three‐dimensional structural analysis of papillary thyroid carcinoma nuclei with serial block‐face scanning electron microscopy (SBF‐SEM)

Three‐dimensional structural analysis of papillary thyroid carcinoma nuclei with serial block‐face scanning electron microscopy (SBF‐SEM)

Differential Gene Expression and Methylation Analysis of Melanoma in TCGA Database to Further Study the Expression Pattern of KYNU in Melanoma

Nuclear Pseudoinclusions and Intranuclear Grooves Have an Important Impact on the Long-term Survival of Patients With Uveal Melanoma

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