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Methods in Molecular Biology (Clifton,... 2023Cellular division is a fundamental process of cellular growth. First, cells replicate their DNA in S phase and then undergo mitosis which, under normal conditions, leads...
Cellular division is a fundamental process of cellular growth. First, cells replicate their DNA in S phase and then undergo mitosis which, under normal conditions, leads to complete cell division. Moreover, mitotic activity correlates to cellular growth activity. The simplest and classical method to measure mitotic activity (mitotic index (MI)), is the manual counting of mitotic cells among a given cell population of interest. The latter can be accomplished via phase contrast microscope observation. However, Giemsa staining may improve accuracy and consistency. Fluorescence immunostaining targeting specific phosphorylations of proteins at critical cell cycle steps will provide further improved analysis via high-throughput capacity of flow or imaging cytometer. Finally, time lapse image analysis provides quantitative and qualitative metrics delineating the process of cellular division including timing of division, duration of mitosis, and failure to procced through or complete mitosis.
Topics: Cell Cycle; Mitosis; Mitotic Index; Phosphorylation; S Phase
PubMed: 36066706
DOI: 10.1007/978-1-0716-2433-3_3 -
Veterinary Pathology Mar 2015Feline mammary carcinoma is highly malignant and generally associated with a poor prognosis, although studies suggest the range of survival times in affected cats is...
Feline mammary carcinoma is highly malignant and generally associated with a poor prognosis, although studies suggest the range of survival times in affected cats is broad. Histologic grading of these tumors is achieved using the Elston and Ellis system, originally developed for human breast cancer. In cats, however, classification using this method has variable prognostic value. Therefore, objectives of this study were (1) to evaluate the Elston and Ellis grading system for feline mammary carcinoma in a predominantly spayed population and (2) to determine whether modification of this system or development of a novel system improved the prognostic value of histologic grading. Survey data and histologic features for 108 carcinomas from 97 cats were analyzed with respect to overall survival. Elston and Ellis grading failed to correlate significantly with overall survival. Using multivariable analysis, lymphovascular invasion, nuclear form, and mitotic count each demonstrated independent prognostic significance (P = .008, <.001, and .004, respectively). Modifications of the Elston and Ellis system and a novel grading system were proposed based on these results; all showed significant correlation with overall survival (P < .001). Median survival times were 27, 29, or 31 months for grade I; 14, 12, or 14 months for grade II; and 13, 5, or 8 months for grade III carcinomas using the mitotic-modified Elston and Ellis, the revised Elston and Ellis, or the novel grading system, respectively. Based on this retrospective study, adoption of the species-specific systems as proposed here may improve the prognostic value of histologic grading for feline mammary carcinoma.
Topics: Animals; Carcinoma; Cat Diseases; Cats; Female; Mammary Neoplasms, Animal; Mitotic Index; Neoplasm Grading; Prognosis; Retrospective Studies; Species Specificity; Survival Analysis
PubMed: 25060990
DOI: 10.1177/0300985814543198 -
The Surgical Clinics of North America Feb 2020The melanoma expert panel devised the evidence-based eighth edition American Joint Committee on Cancer staging system by conducting vigorous analyses of stage I, II, and... (Review)
Review
The melanoma expert panel devised the evidence-based eighth edition American Joint Committee on Cancer staging system by conducting vigorous analyses of stage I, II, and III patients from the International Melanoma Database and Discovery Platform. Key changes in the eighth edition are regarding subcategorization of T1, M1, pathologic stage grouping of stage I and III, and refining the definitions and terminologies used in the staging system. As the knowledge of tumor biology improves, the staging of melanoma will continue to evolve to enable betterment of care.
Topics: Humans; Melanoma; Mitotic Index; Neoplasm Staging; Prognosis; Skin Neoplasms
PubMed: 31753114
DOI: 10.1016/j.suc.2019.09.007 -
Current Gastroenterology Reports Aug 2020Gastroesophageal neuroendocrine neoplasms (NENs) are a rare entity. Recent 2019 WHO classifications reflect our understanding of tumor biology, namely, that distinct... (Review)
Review
PURPOSE OF REVIEW
Gastroesophageal neuroendocrine neoplasms (NENs) are a rare entity. Recent 2019 WHO classifications reflect our understanding of tumor biology, namely, that distinct molecular characteristics underline tumor behavior and prognosis. Here, we reviewed the evidence for linking molecular findings with the clinicopathological features and treatment of gastroesophageal NENs.
RECENT FINDINGS
Degree of differentiation and Ki-67 proliferation index are required for accurate classification of neuroendocrine tumors and carcinomas but not sufficient to distinguish between the two entities. Resection remains the mainstay treatment for early-stage gastroesophageal neuroendocrine tumors. Additional perioperative therapy may benefit mitotically active tumors. There is a role for somatostatin analogues, especially in the setting of metastatic and symptomatic disease. New radiolabeled somatostatin analogues, immunotherapy, and embolization offer multimodality treatments for distant metastases. We need to understand the specific underlying biology of the various subtypes of gastroesophageal NENs to provide tailored treatment.
Topics: Esophageal Neoplasms; Humans; Mitotic Index; Neoplasm Grading; Neoplasm Staging; Neoplasms, Complex and Mixed; Neuroendocrine Tumors; Prognosis; Stomach Neoplasms
PubMed: 32797314
DOI: 10.1007/s11894-020-00788-w -
Modern Pathology : An Official Journal... Sep 2021Mitoses are often assessed by pathologists to assist the diagnosis of cancer, and to grade malignancy, informing prognosis. Historically, this has been done by... (Review)
Review
Mitoses are often assessed by pathologists to assist the diagnosis of cancer, and to grade malignancy, informing prognosis. Historically, this has been done by expressing the number of mitoses per n high power fields (HPFs), ignoring the fact that microscope fields may differ substantially, even at the same high power (×400) magnification. Despite a requirement to define HPF size in scientific papers, many authors fail to address this issue adequately. The problem is compounded by the switch to digital pathology systems, where ×400 equivalent fields are rectangular and also vary in the area displayed. The potential for error is considerable, and at times this may affect patient care. This is easily solved by the use of standardized international (SI) units. We, therefore, recommend that features such as mitoses are always counted per mm, with an indication of the area to be counted and the method used (usually "hotspot" or "average") to obtain the results.
Topics: Humans; Microscopy; Mitotic Index; Neoplasms
PubMed: 34079071
DOI: 10.1038/s41379-021-00825-7 -
International Journal of Surgical... Sep 2023Snail family transcriptional repressor 2 (SNAI2, Slug) is a transcription factor that belong to the Slug/Snail superfamily. Site specific phosphorylation of slug (pSlug)...
Snail family transcriptional repressor 2 (SNAI2, Slug) is a transcription factor that belong to the Slug/Snail superfamily. Site specific phosphorylation of slug (pSlug) is detected during the M phase, and thus, this phosphorylated protein is considered a novel marker for detecting mitotic figures. Herein, we investigated whether the detection of mitosis using pSlug expression can be used in the histological grading of meningioma. We performed immunohistochemistry for pSlug and PHH3 in tissue samples of 61 patients with meningioma and examined the association between mitotic counts using pSlug and recurrence-free survival (RFS). The nuclear expression of pSlug was observed in the cell with mitotic figures. Tumor grading based on pSlug was significantly associated with the RFS ( < .001). It can be concluded that pSlug is a useful and practical marker to detect mitosis and seems to be reliable for the counting of mitoses in histological grading of meningioma.
Topics: Humans; Meningioma; Histones; Mitotic Index; Immunohistochemistry; Mitosis; Neoplasm Grading; Meningeal Neoplasms; Biomarkers, Tumor
PubMed: 36172742
DOI: 10.1177/10668969221126121 -
Veterinary Pathology Nov 2018
Topics: Animals; Biopsy, Fine-Needle; Carcinoma, Hepatocellular; Dog Diseases; Dogs; Female; Liver; Liver Neoplasms; Mitotic Index; Observer Variation
PubMed: 30381035
DOI: 10.1177/0300985818789478 -
Monographs in Clinical Cytology 2018
Review
Topics: B-Lymphocytes; Biopsy, Fine-Needle; Histiocytes; Humans; Lymph Nodes; Lymphatic Vessels; Lymphoproliferative Disorders; Mitotic Index; Plasma Cells; Staining and Labeling; Tissue Fixation
PubMed: 29131003
DOI: 10.1159/000478878 -
Journal of Comparative Pathology Nov 2021Gastrointestinal lymphomas are uncommon in dogs and little is known about their distinct subtypes or proliferation rate. The aim of this study was to stratify 33 canine...
Gastrointestinal lymphomas are uncommon in dogs and little is known about their distinct subtypes or proliferation rate. The aim of this study was to stratify 33 canine gastrointestinal lymphoma samples according to the latest World Health Organization classification and to determine the Ki67 proliferation index by manual counting, digital image analysis and visual estimation. The Ki67 index was then correlated with subtype, immunophenotype, mitotic index, grade and tumour location. The mitotic index correlated positively with the Ki67 index. A significantly higher number of Ki67-positive cells was found in enteropathy-associated T-cell lymphoma type I and in diffuse large B-cell lymphoma compared with enteropathy-associated T-cell lymphoma type II. There was also a significant difference in Ki67 immunolabelled cells between grade 1 and grade 2 lymphomas. Moderate agreement was found between the Ki67 index as obtained by manual counting and visual estimation, but there was strong agreement between manual counting and digital image analysis. The user-friendly digital imaging system used in this study could have potential for future determination of the Ki67 index in lymphoid neoplasms.
Topics: Animals; Cell Proliferation; Dog Diseases; Dogs; Gastrointestinal Neoplasms; Ki-67 Antigen; Lymphoma, Large B-Cell, Diffuse; Mitotic Index
PubMed: 34886989
DOI: 10.1016/j.jcpa.2021.10.003 -
Drug and Chemical Toxicology Nov 2021In a previous study, 3-amino-4-[4-(dimethylamino)phenyl]-4,5-dihydro-1,2,5-thiadiazole 1,1-dioxide (DPTD), which is five-membered cyclosulfamide, was synthesized and...
In a previous study, 3-amino-4-[4-(dimethylamino)phenyl]-4,5-dihydro-1,2,5-thiadiazole 1,1-dioxide (DPTD), which is five-membered cyclosulfamide, was synthesized and structurally characterized. The aim of this study was to investigate the cytotoxic and genotoxic effects of DPTD on cultured human lymphocytes in the presence and absence of a metabolic activation system (S9 mix). The cytotoxicity and genotoxicity of DPTD in human peripheral blood lymphocytes were examined by using chromosomal aberration (CA) and micronucleus (MN) tests. Mitomycin-C (MMC) for cultures without S9 mix and cyclophosphamide monohydrate (CP) for cultures with S9 mix were used as positive controls. The cultures were treated with DPTD (45, 90, and 180 µg/mL) in the absence and presence of S9 mix. The cells were also co-treated with DPTD together with MMC or CP. DPTD showed cytotoxic activity due to decreases in mitotic index (MI) and nuclear division index (NDI) in the absence and presence of S9 mix. DPTD also increased the CAs, aberrant cells with CAs and MN values in cultures with and without S9 mix. When DPTD and MMC or CP were used together, lower MI and NDI values and higher CA and MN values were found than those DPTD treated alone. Both DPTD and its metabolites have cytotoxic, cytostatic and genotoxic potential on human peripheral blood lymphocyte cultures under the experimental conditions. Furthermore, co-treatment of DPTD and MMC or CP can cause more cytotoxicity and genotoxicity. Our results indicated that the use of DPTD with other chemotherapeutic drugs may display more effective results.
Topics: Cells, Cultured; Chromosome Aberrations; Humans; Lymphocytes; Micronucleus Tests; Mitotic Index; Mutagens; Sister Chromatid Exchange; Thiadiazoles
PubMed: 31621427
DOI: 10.1080/01480545.2019.1677703