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Solitary fibrous tumor: a clinicopathological study of 110 cases and proposed risk assessment model.Modern Pathology : An Official Journal... Sep 2012Solitary fibrous tumor represents a spectrum of mesenchymal tumors, encompassing tumors previously termed hemangiopericytoma, which are classified as having intermediate...
Solitary fibrous tumor represents a spectrum of mesenchymal tumors, encompassing tumors previously termed hemangiopericytoma, which are classified as having intermediate biological potential (rarely metastasizing) in the 2002 World Health Organization classification scheme. Few series have reported on clinicopathological predictors with outcome data and formal statistical analysis in a large series of primary tumors as a single unified entity. Institutional pathology records were reviewed to identify primary solitary fibrous tumor cases, and histological sections and clinical records reviewed for canonical prognostic indicators, including patient age, tumor size, mitotic index, tumor cellularity, nuclear pleomorphism, and tumor necrosis. Patients (n=103) with resected primary solitary fibrous tumor were identified (excluding meningeal tumors). The most common sites of occurrence were abdomen and pleura; these tumors were larger than those occurring in the extremities, head and neck or trunk, but did not demonstrate significant outcome differences. Overall 5- and 10-year metastasis-free rates were 74 and 55%, respectively, while 5- and 10-year disease-specific survival rates were 89 and 73%. Patient age, tumor size, and mitotic index predicted both time to metastasis and disease-specific mortality, while necrosis predicted metastasis only. A risk stratification model based on age, size, and mitotic index clearly delineated patients at high risk for poor outcomes. While small tumors with low mitotic rates are highly unlikely to metastasize, large tumors ≥ 15 cm, which occur in patients ≥ 55 years, with mitotic figures ≥ 4/10 high-power fields require close follow-up and have a high risk of both metastasis and death.
Topics: Abdominal Neoplasms; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Mitotic Index; Models, Biological; Pleural Neoplasms; Risk Assessment; Solitary Fibrous Tumor, Pleural; Survival Rate; Young Adult
PubMed: 22575866
DOI: 10.1038/modpathol.2012.83 -
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 -
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 -
Annals of Oncology : Official Journal... Sep 2013In a retrospective study on node-negative breast cancer, a prognostic index consisting of a proliferation factor, S-phase fraction (SPF), progesterone receptor status... (Clinical Trial)
Clinical Trial
A prospective, multicenter validation study of a prognostic index composed of S-phase fraction, progesterone receptor status, and tumour size predicts survival in node-negative breast cancer patients: NNBC, the node-negative breast cancer trial.
BACKGROUND
In a retrospective study on node-negative breast cancer, a prognostic index consisting of a proliferation factor, S-phase fraction (SPF), progesterone receptor status (PR), and tumour size identified one-third of patients as high risk, with a sixfold increased risk of breast cancer death. This prospective multicenter cohort study was set up to validate the index.
PATIENTS AND METHODS
In 576 T1-2N0 patients <60 years, prospective analyses of PR and SPF were carried out. High risk was defined as ≥2 of the following: size >20 mm, PR-negativity, and high SPF (in the absence of SPF, Bloom-Richardson grade 3). Median follow-up was 17.8 years.
RESULTS
Thirty-one percent were high risk. In univariate analysis, the index was prognostic for breast cancer-specific survival after 5 years [hazard ratio (HR) = 4.7, 95% confidence interval (95% CI) 2.5-8.9], 10 years (HR = 2.2, 95% CI 1.5-3.3), and 15 years (HR = 1.7, 95% CI 1.2-2.5), and remained significant after adjustment for adjuvant medical treatment and age. In the 37% of patients with no risk factors, only one patient died of breast cancer the first 5 years.
CONCLUSIONS
This prospective study validates a prognostic index consisting of a proliferation factor, PR-status, and tumour size. The index may be helpful for prognostic considerations and for selection of patients in need of adjuvant therapy.
Topics: Biomarkers, Tumor; Breast Neoplasms; Cell Proliferation; Cohort Studies; Disease-Free Survival; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Mitotic Index; Prospective Studies; Receptors, Progesterone; S Phase; Survival
PubMed: 23704202
DOI: 10.1093/annonc/mdt186 -
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 -
Neuro-oncology Aug 2023
Topics: Humans; Prognosis; Isocitrate Dehydrogenase; Mitotic Index; Homozygote; Consensus; Sequence Deletion; Astrocytoma; Brain Neoplasms; Cyclin-Dependent Kinase Inhibitor p16
PubMed: 37097042
DOI: 10.1093/neuonc/noad063 -
Breast Cancer Research : BCR 2006Various methods are available for the measurement of proliferation rates in tumours, including mitotic counts, estimation of the fraction of cells in S-phase of the cell... (Review)
Review
Various methods are available for the measurement of proliferation rates in tumours, including mitotic counts, estimation of the fraction of cells in S-phase of the cell cycle and immunohistochemistry of proliferation-associated antigens. The evidence, advantages and disadvantages for each of these methods along with other novel approaches is reviewed in relation to breast cancer. The potential clinical applications of proliferative indices are discussed, including their use as prognostic indicators and predictors of response to systemic therapy.
Topics: Antigens, Nuclear; Breast Neoplasms; Cell Proliferation; Cyclin-Dependent Kinases; Cyclins; DNA Topoisomerases, Type II; Deuterium Oxide; Disease Progression; Female; Humans; Ki-67 Antigen; Mitotic Index; Nuclear Proteins; Positron-Emission Tomography; Proliferating Cell Nuclear Antigen; S Phase; Thymidine Kinase; Tissue Array Analysis
PubMed: 17164010
DOI: 10.1186/bcr1618 -
Journal of Clinical Pathology Jul 2004Breast cancer is the leading cause of death among solid tumours in women, and its incidence is increasing in the West. Adjuvant chemotherapy and hormonal treatment... (Review)
Review
Breast cancer is the leading cause of death among solid tumours in women, and its incidence is increasing in the West. Adjuvant chemotherapy and hormonal treatment improve survival but have potentially serious side effects, and are costly. Because adjuvant treatment should be given to high risk patients only, and traditional prognostic factors (lymph node status, tumour size) are insufficiently accurate, better predictors of high risk and treatment response are needed. Invasive breast cancer metastasises haematogenously very early on, so many breast cancer prognosticators are directly or indirectly related to proliferation. Although studies evaluating the role of individual proliferation regulating genes have greatly increased our knowledge of this complex process, the functional end result-cells dividing-has remained the most important prognostic factor. This article reviews the prognostic value of different proliferation assays in invasive breast cancer, and concludes that increased proliferation correlates strongly with poor prognosis, irrespective of the methodology used. Mitosis counting provides the most reproducible and independent prognostic value, and Ki67/MIB1 labelling and cyclin A index are promising alternatives that need methodological fine tuning.
Topics: Biomarkers, Tumor; Breast Neoplasms; Cell Division; Female; Humans; Mitotic Index; Neoplasm Invasiveness; Prognosis
PubMed: 15220356
DOI: 10.1136/jcp.2003.010777 -
Annals of Surgery Jan 2002To review the published literature on prognostic factors in patients with node-negative breast cancer, focusing principally on recent studies with large sample sizes and... (Comparative Study)
Comparative Study Review
OBJECTIVE
To review the published literature on prognostic factors in patients with node-negative breast cancer, focusing principally on recent studies with large sample sizes and extended follow-up periods.
SUMMARY BACKGROUND DATA
Although numerous studies have examined prognostic factors in patients with breast cancer, relatively few have dealt specifically with node-negative disease, and interpretation has been limited by small sample size and limited follow-up times.
METHODS
A review of the Medline database from 1996 to 2000 was undertaken, with additional papers published before 1996 identified through review articles. For inclusion in the analysis, papers needed to meet the following core criteria: 200 or more node-negative patients with invasive breast carcinoma; median follow-up time at least 5 years; method of testing and cut-off points specified; overall survival and/or disease-free survival specified; and relative risk or statistical probability values given for comparisons.
RESULTS
Three or more papers that met the core criteria were retrieved for each of 11 potential prognostic factors. Of these, tumor size, tumor grade, cathepsin-D, Ki-67, S-phase fraction, mitotic index, and vascular invasion showed a significant association with survival outcomes; HER2/neu and DNA ploidy showed no significant association; and estrogen receptor status and p53 showed mixed results. Lack of standardization in measurement techniques for many of the markers, including cathepsin-D, Ki-67, HER2/neu, and p53, limited their current clinical usefulness.
CONCLUSIONS
In large studies with extended follow-up periods, tumor size, tumor grade, cathepsin-D, Ki-67, S-phase fraction, mitotic index, and vascular invasion showed a significant association with survival outcome measures in patients with early-stage node-negative breast cancer. Because of technical difficulties and variations in the measurement of many of these factors, tumor size and tumor grade remain the only markers that currently have broad clinical usefulness for this patient group.
Topics: Analysis of Variance; Biomarkers, Tumor; Breast Neoplasms; Cathepsin D; DNA; Disease-Free Survival; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Genes, erbB-2; Genes, p53; Genetic Predisposition to Disease; Humans; Ki-67 Antigen; Lymph Nodes; Mitotic Index; Multivariate Analysis; Mutation; Ploidies; Probability; Prognosis; Receptors, Estrogen; Risk; Risk Factors; S Phase; Survival Analysis; Time Factors
PubMed: 11753038
DOI: 10.1097/00000658-200201000-00003 -
Mutation Research 2009Higher plants are recognized as excellent genetic models to detect environmental mutagens and are frequently used in monitoring studies. Among the plant species, Alium... (Review)
Review
Higher plants are recognized as excellent genetic models to detect environmental mutagens and are frequently used in monitoring studies. Among the plant species, Alium cepa has been used to evaluate DNA damages, such as chromosome aberrations and disturbances in the mitotic cycle. Employing the A. cepa as a test system to detect mutagens dates back to the 40s. It has been used to this day to assess a great number of chemical agents, which contributes to its increasing application in environmental monitoring. The A. cepa is characterized as a low cost test. It is easily handled and has advantages over other short-term tests that require previous preparations of tested samples, as well as the addition of exogenous metabolic system. Higher plants, even showing low concentrations of oxidase enzymes and a limitation in the substrate specification in relation to other organism groups, present consistent results that may serve as a warning to other biological systems, since the target is DNA, common to all organisms. The A. cepa test also enables the evaluation of different endpoints. Among the endpoints, chromosome aberrations have been the most used one to detect genotoxicity along the years. The mitotic index and some nuclear abnormalities are used to evaluate citotoxicity and analyze micronucleus to verify mutagenicity of different chemicals. Moreover, the A. cepa test system provides important information to evaluate action mechanisms of an agent about its effects on the genetic material (clastogenic and/or aneugenic effects). In the face of all the advantages that the A. cepa test system offers, it has been widely used to assess the impacts caused by xenobiotics, characterizing an important tool for environmental monitoring studies, where satisfactory results have been reported.
Topics: Chromosome Aberrations; Environmental Monitoring; Environmental Pollutants; Micronucleus Tests; Mitotic Index; Mutagenicity Tests; Mutagens; Onions; Sensitivity and Specificity
PubMed: 19577002
DOI: 10.1016/j.mrrev.2009.06.002