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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 -
Neuro-oncology May 2015
Topics: Biomarkers, Tumor; Female; Histones; Humans; Male; Meningioma; Mitosis; Mitotic Index
PubMed: 25813470
DOI: 10.1093/neuonc/nov047 -
Virchows Archiv : An International... Jul 2023The use of adjuvant radiotherapy is controversial for atypical meningiomas undergoing gross total resection. It has recently been proposed that meningiomas may be...
Atypical meningiomas with an immunohistochemical profile consistent with hypermetabolic or proliferative molecular groups show high mitotic index, chromosomal instability, and higher recurrence risk.
The use of adjuvant radiotherapy is controversial for atypical meningiomas undergoing gross total resection. It has recently been proposed that meningiomas may be classified into four molecular groups (MG): immunogenic (MG1), benign NF2-wildtype (MG2), hypermetabolic (MG3), and proliferative (MG4). The two latter have the worst prognosis, and it has been suggested that they can be identified using ACADL and MCM2 immunostainings. We studied 55 primary atypical meningiomas, treated with gross total resection and no adjuvant therapies, to assess whether ACADL and MCM2 immuno-expression may identify patients at higher recurrence risk, thus requiring adjuvant treatments. Twelve cases resulted ACADL-/MCM2-, 9 ACADL + /MCM2-, 17 ACADL + /MCM2 + , and 17 ACADL-/MCM2 + . MCM2 + meningiomas displayed more frequent atypical features (prominent nucleoli, small cells with high nuclear-to-cytoplasmic ratio) and CDKN2A hemizygous deletion (HeDe) (P = 0.011). The immunoexpression of ACADL and/or MCM2 was significantly associated with higher mitotic index, 1p and 18q deletions, increased recurrence rate (P = 0.0006), and shorter recurrence-free survival (RFS) (P = 0.032). At multivariate analysis, carried out including ACADL/MCM2 immuno-expression, mitotic index, and CDKN2A HeDe as covariates, this latter resulted a significant and independent prognosticator of shorter RFS (P = 0.0003).
Topics: Humans; Meningioma; Meningeal Neoplasms; Mitotic Index; Radiotherapy, Adjuvant; Chromosomal Instability; Neoplasm Recurrence, Local; Retrospective Studies
PubMed: 37014425
DOI: 10.1007/s00428-023-03537-2 -
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 -
Ecotoxicology and Environmental Safety Apr 2021The rampant use of pesticides can cause serious environmental problems. They can be contaminating surface water and groundwater, affecting the surrounding micro and...
The rampant use of pesticides can cause serious environmental problems. They can be contaminating surface water and groundwater, affecting the surrounding micro and macro biota. In this sense, this work aimed to evaluate the effects of a tebuconazole-based fungicide through endpoints accessed in Lactuca sativa bioassays. Germinated-seeds with roots upon 2 mm were treated with a fungicide containing Tebuconazole (TBZ) as active compound. The final concentration of TBZ in the tested solutions were 0.025 (C1); 0.05 (C2); 0.1 (C3); 0.2 (C4) and 0.4 g/L (C5). L. sativa roots were exposed for 24 h to these solutions and Petri dishes containing the treated seeds were kept in incubation chamber at 24 °C. Two positive controls (PC,) the herbicide trifluralin (0.84 mg/L) and Methanesulfonate (4 ×10 mol/L), were applied. Distilled water was negative control (NC). The following endpoints were analyzed: root growth (RG), cytogenotoxic potential by cell cycle analysis, induction of DNA damage through TUNEL and comet assays. The obtained data were submitted to one-way variance analysis (ANOVA) and then to Tukey or Kruskal Wallis (P < 0.05) tests. The concentrations (C1, C2, C4 and C5) affected negatively the RG of L. sativa, in comparison with the NC. The mitotic index was reduced by 25% from NC to C1 and in the rest of treatments it did not present significant modifications. However, from C3 to C5 great amount of chromosome alterations were observed, in comparison with the NC. TBZ-based fungicide also induced DNA fragmentation as measured by TUNEL and comet assays. Thus, TBZ-based fungicide in some concentrations can have phytotoxic, cytotoxic and genotoxic effects in roots and meristematic cells of L. sativa.
Topics: Biological Assay; Chromosome Aberrations; Comet Assay; DNA Damage; Fungicides, Industrial; Germination; Herbicides; Lactuca; Meristem; Mitotic Index; Plant Roots; Seeds; Toxicogenetics; Triazoles
PubMed: 33578099
DOI: 10.1016/j.ecoenv.2021.111985 -
Head and Neck Pathology Jun 2021Myoepithelial neoplasms are rare tumors of the salivary glands with predominant myoepithelial differentiation and a broad histologic spectrum. Their histological...
Myoepithelial neoplasms are rare tumors of the salivary glands with predominant myoepithelial differentiation and a broad histologic spectrum. Their histological features, immunohistochemical profile and biological behavior are not well characterized and pose a diagnostic challenge. A total of 15 myoepithelial tumors, diagnosed during 2012 and 2019 were subcategorized and correlated with MIB-1 labeling index (LI) and various histological parameters. Immunohistochemical stains for MIB-1 and other antibodies were performed. Statistical analysis was done by chi-square test, Fisher's exact test and Kaplan Meier curve. Nine patients were male and six were female with the median age of 44 years (range 21-83 years). Of the 15 patients, 6 cases were classified as myoepithelioma (ME) and 9 cases as myoepithelial carcinoma (MECA). Parotid gland was the most common site (46.7%) followed by the palate. MEs showed well circumscribed tumor borders whereas MECAs exhibited focal capsular to extensive invasion into adjacent tissues. Epithelioid cell morphology was most common followed by mixed cell morphology. MIB-1 LI was significantly associated with invasive tumor borders, necrosis and high mitosis. Increased frequency of recurrence was noted with high MIB-1 LI, though it was not statistically significant. MIB-1 LI was high in nearly all MECAs with focal capsular to extensive invasion while low in MEs. Myoepithelial tumor with multinodular growth pattern and focal capsular invasion may have an indolent behavior if mitotic activity and MIB-1 LI is low. Early diagnosis and treatment of MECAs significantly improves the patient's survival and prognosis.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Antinuclear; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma; Female; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Middle Aged; Mitotic Index; Myoepithelioma; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Salivary Gland Neoplasms
PubMed: 32959208
DOI: 10.1007/s12105-020-01225-0 -
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 -
Archives of Pathology & Laboratory... Apr 2008Smooth muscle tumors (SMTs) are the most frequent mesenchymal tumors of the uterus. The majority of the uterine SMTs are readily classificable as benign or malignant... (Review)
Review
Smooth muscle tumors (SMTs) are the most frequent mesenchymal tumors of the uterus. The majority of the uterine SMTs are readily classificable as benign or malignant based on their gross and microscopic appearances. However, when unusual features are seen in some leiomyoma variants, the differential diagnosis with a leiomyosarcoma may become challenging. Moreover, diagnostic criteria for the different subtypes of leiomyosarcoma are not uniform. Finally, non-smooth muscle tumors that originate in the uterus may show overlapping histologic and even immunohistochemical features with uterine SMTs, more commonly with the spindle and epithelioid variants, complicating their correct classification. The diagnosis of malignant uterine SMTs has important prognostic and therapeutic implications. This review provides a practical approach to the diagnosis of uterine leiomyosarcoma based on a systematic assessment of histologic parameters as well as a systematic approach to its differential diagnosis based on histologic and immunohistochemical features.
Topics: Female; Humans; Leiomyosarcoma; Mitotic Index; Necrosis; Pathology; Smooth Muscle Tumor; Uterine Neoplasms
PubMed: 18384211
DOI: 10.5858/2008-132-595-SMTOTU -
Virchows Archiv : An International... Oct 2006The need for standards in the management of patients with endocrine tumors of the digestive system prompted the European Neuroendocrine Tumor Society (ENETS) to organize...
The need for standards in the management of patients with endocrine tumors of the digestive system prompted the European Neuroendocrine Tumor Society (ENETS) to organize a first Consensus Conference, which was held in Frascati (Rome) and was based on the recently published ENETS guidelines on the diagnosis and treatment of digestive neuroendocrine tumors (NET). Here, we report the tumor-node-metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that was designed, discussed, and consensually approved at this conference. In addition, we report the proposal for a working formulation for the grading of digestive NETs based on mitotic count and Ki-67 index. This proposal, which needs to be validated, is meant to help clinicians in the stratification, treatment, and follow-up of patients.
Topics: Biomarkers, Tumor; Digestive System Neoplasms; Humans; Lymph Nodes; Mitotic Index; Neoplasm Metastasis; Neoplasm Staging; Neuroendocrine Tumors
PubMed: 16967267
DOI: 10.1007/s00428-006-0250-1