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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 -
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 -
Revista Espanola de Patologia :... 2021The mitotic count (MC), number of mitosis per unit area, is a very important parameter frequently used for classification and grading of some tumors. Traditionally, the...
PURPOSE
The mitotic count (MC), number of mitosis per unit area, is a very important parameter frequently used for classification and grading of some tumors. Traditionally, the MC has been expressed in terms of number of mitoses per high power field. The size of the field of view can vary greatly among different microscopes. In order to avoid under or overestimation of mitotic count, a conversion needs to be made.
METHODS
A simple formula based on a simple rule of three has been devised to standardize the mitotic count to the reference area by multiplying the number of mitotic figures by a correction factor which has been calculated for the most frequently used microscopes and various common tumors.
RESULTS AND CONCLUSIONS
We propose this simple method, which involves only a single multiplication, to standardize the mitotic count to the reference area.
Topics: Algorithms; Humans; Microscopy; Mitotic Index; Neoplasm Grading; Neoplasm Staging; Neoplasms
PubMed: 33455692
DOI: 10.1016/j.patol.2020.06.011 -
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 -
Nature Cell Biology Mar 2022
Topics: Cell Proliferation; Humans; Mitotic Index; Neoplasms
PubMed: 35292782
DOI: 10.1038/s41556-022-00862-7 -
The Breast Journal 2001Proliferative activity has been proven to be of prognostic significance in breast carcinoma. This study was performed to compare the different proliferative fractions in... (Comparative Study)
Comparative Study
Proliferative activity has been proven to be of prognostic significance in breast carcinoma. This study was performed to compare the different proliferative fractions in the Egyptian population and to define the most suitable one for daily routine use in our surgical pathology laboratories. The proliferative activity of 63 invasive ductal carcinomas was evaluated by immunohistochemical staining of paraffin-embedded tissue sections with MIB-1 rabbit polyclonal antibody and the heat-induced epitope retrieval method, flow cytometric determination of the S-phase fraction (SPF) on frozen tissues, and estimation of the Scarff-Bloom-Richardson (SBR) grading and mitotic figure count (MFC) on hematoxylin and eosin-stained tissue sections. Fifty-two percent of invasive ductal carcinoma were aneuploid. The mean values of MIB-1 index, SPF, and MFC were 17.7 +/- 12.3, 4.9 +/- 3.8, and 5.2 +/- 4.5, respectively, for diploid tumors; while for aneuploid tumors, they were 58.6 +/- 31.9, 19.9 +/- 12.2, and 23.1 +/- 16.9, respectively. These values were significantly higher in aneuploid versus diploid tumors (p < 0.0001). A close correlation was found between MIB-1 index, SPF, MFC, and SBR grading (p < 0.0001). In conclusion, in surgical pathology laboratories that cannot afford the costs of flow cytometry and/or immunostaining, proper SBR grading and MFC can provide an estimation of the proliferation fraction similar to the flow cytometric SPF and MIB-1 immunostaining.
Topics: Antigens, Nuclear; Biopsy; Breast Neoplasms; Cell Differentiation; Egypt; Female; Humans; Ki-67 Antigen; Mitotic Index; Nuclear Proteins; Predictive Value of Tests; S Phase
PubMed: 11328317
DOI: 10.1046/j.1524-4741.2001.007002106.x -
Human Pathology Sep 1999
Topics: Breast Neoplasms; Female; Humans; Mathematics; Mitotic Index
PubMed: 10492050
DOI: 10.1016/s0046-8177(99)90234-4 -
The American Journal of Pathology Oct 1998
Review
Topics: Animals; Apoptosis; DNA, Neoplasm; Humans; Mitotic Index; Necrosis; Neoplasms
PubMed: 9777936
DOI: 10.1016/S0002-9440(10)65649-0 -
Anticancer Research 2004The study was designed in order to evaluate the degree of correlation of mitotic index (MI), Ki67 (MIB1) score and S-phase fraction (SPF) as markers of cell...
Analysis of correlation between mitotic index, MIB1 score and S-phase fraction as proliferation markers in invasive breast carcinoma. Methodological aspects and prognostic value in a series of 257 cases.
BACKGROUND
The study was designed in order to evaluate the degree of correlation of mitotic index (MI), Ki67 (MIB1) score and S-phase fraction (SPF) as markers of cell proliferation and prognosis in breast cancer.
MATERIALS AND METHODS
The series analysed corresponded to 257 consecutive invasive breast carcinoma, treated at the Institut Curie, France, in 1995. Nottingham histological grade and MIB1 semiquantitative and quantitative score were assessed on histological sections, whereas SPF was calculated using flow cytometry analysis of fine-needle aspiration products. Proliferation indices were compared to pathological data and to overall survival (OS) and disease-free survival (DFS) (minimum follow-up: 72 months).
RESULTS
The median values for the proliferation markers were 9/10 HPF for MI, 32.4% for MIB1 and 3.7% for SPF. A high rate of correlation (r=0.96; p<0.001) was observed between semi-quantitative and quantitative MIBI evaluation. A positive correlation was found between the three markers (r ranging from 0.54 to 0.61;p<0.001). Univariate analysis of markers associated to disease outcome showed that MIB1, axillary node status (N) and progesterone receptor (PR) status were significantly associated with OS and that MIB1 and SPF were associated with DFS, together with node and hormone receptor status. In multivariate analysis, when proliferation markers were adjusted on the N and PR status, only MIB1 retained a prognostic value for OS (RR= 1.83) [1.00;3.35] and SPF for DFS (RR= 1.58) [1.02-2.44] (p=0.04).
CONCLUSION
A good level of correlation was observed between the values of the three markers of tumour cell proliferation analysed. In this series of invasive breast cancers, MIB1 immunostaining was found to be a prognostic marker of both OS and DFS. The median (32.4%) was a valuable cut-off value for prognostic assessment. Semi-quantitative and quantitative evaluations provided very similar values. MIB1 can thus be considered as a reliable prognostic maker, usable in small size tissue specimens which are inappropriate for MI or SPF analysis. The impact of MIB1 compared to that of the other proliferative markers will be further assessed in a subgroup of T1N0M0 for which the prognostic assessment is of major interest.
Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Cell Division; Disease-Free Survival; Humans; Ki-67 Antigen; Middle Aged; Mitotic Index; Neoplasm Staging; Prognosis; S Phase
PubMed: 15510624
DOI: No ID Found -
Veterinary Pathology Jan 2016
Topics: Animals; Ki-67 Antigen; Mitotic Index
PubMed: 26712813
DOI: 10.1177/0300985815593349