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Virchows Archiv : An International... Jan 2024Oral epithelial dysplasia (OED) is diagnosed and graded using a range of histological features, making grading subjective and challenging. Mitotic counting and...
Oral epithelial dysplasia (OED) is diagnosed and graded using a range of histological features, making grading subjective and challenging. Mitotic counting and phosphohistone-H3 (PHH3) staining have been used for the prognostication of various malignancies; however, their importance in OED remains unexplored. This study conducts a quantitative analysis of mitotic activity in OED using both haematoxylin and eosin (H&E)-stained slides and immunohistochemical (IHC) staining for PHH3. Specifically, the diagnostic and prognostic importance of mitotic number, mitotic type and intra-epithelial location is evaluated. Whole slide images (WSI) of OED (n = 60) and non-dysplastic tissue (n = 8) were prepared for analysis. Five-year follow-up data was collected. The total number of mitosis (TNOM), mitosis type and intra-epithelial location was manually evaluated on H&E images and a digital mitotic count performed on PHH3-stained WSI. Statistical associations between these features and OED grade, malignant transformation and OED recurrence were determined. Mitosis count increased with grade severity (H&E: p < 0.005; IHC: p < 0.05), and grade-based differences were seen for mitosis type and location (p < 0.05). The ratio of normal-to-abnormal mitoses was higher in OED (1.61) than control (1.25) and reduced with grade severity. TNOM, type and location were better predictors when combined with histological grading, with the most prognostic models demonstrating an AUROC of 0.81 for transformation and 0.78 for recurrence, exceeding conventional grading. Mitosis quantification and PHH3 staining can be an adjunct to conventional H&E assessment and grading for the prediction of OED prognosis. Validation on larger multicentre cohorts is needed to establish these findings.
Topics: Humans; Histones; Prognosis; Mitotic Index; Biomarkers, Tumor; Neoplasm Grading; Mitosis; Phosphorylation
PubMed: 37882821
DOI: 10.1007/s00428-023-03668-6 -
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 -
Polish Archives of Internal Medicine Jun 2018Introduction Adrenocortical carcinoma (ACC) is a rare malignancy, associated with poor outcome and few therapeutic options. Despite increasing attention, the knowledge...
Introduction Adrenocortical carcinoma (ACC) is a rare malignancy, associated with poor outcome and few therapeutic options. Despite increasing attention, the knowledge about the clinical course and treatment of these tumors is limited. Objectives Survival rates in ACC are still low and the percentage of relapse is high. Thus, it is crucial to identify the prognostic factors of overall survival (OS) and recurrence‑free survival (RFS). Patients and methods This was a retrospective analysis of 66 patients diagnosed with ACC between 2002 and 2015. Results The median OS was 43.5 months, 78.19 months for stage I + II, 22.95 months for stage III, and 19.54 months for stage IV ACC. Older age, stage IV ACC, margin status R2, and no mitotane treatment were associated with poor OS. Low Ki67 and mitotic indices were related to improved OS in a univariate analysis. The median RFS was 101.1 months. Disease recurrence after potentially curative surgery was reported in 1 patient (25%) with stage I, 12 patients (46%) with stage II, and 9 patients (45%) with stage III ACC. Male sex and no mitotane treatment were associated with a reduced RFS in a multivariate analysis and higher Ki67 and mitotic indices in the univariate analysis. Conclusions Ki67 and mitotic indices should be considered as prognostic factors when planning the adjuvant treatment of ACC. Mitotane treatment may be independently associated with better outcomes regardless of the tumor stage.
Topics: Adrenocortical Carcinoma; Adult; Aged; Female; Humans; Male; Middle Aged; Mitotane; Mitotic Index; Poland; Prognosis; Retrospective Studies; Survival Rate
PubMed: 29726479
DOI: 10.20452/pamw.4260 -
Hormones & Cancer Jun 201417β-Estradiol (estrogen), through receptor binding and activation, is required for mammary gland development. Estrogen stimulates epithelial proliferation in the...
17β-Estradiol (estrogen), through receptor binding and activation, is required for mammary gland development. Estrogen stimulates epithelial proliferation in the mammary gland, promoting ductal elongation and morphogenesis. In addition to a developmental role, estrogen promotes proliferation in tumorigenic settings, particularly breast cancer. The proliferative effects of estrogen in the normal breast and breast tumors are attributed to estrogen receptor α. Although in vitro studies have demonstrated that the G protein-coupled estrogen receptor (GPER, previously called GPR30) can modulate proliferation in breast cancer cells both positively and negatively depending on cellular context, its role in proliferation in the intact normal or malignant breast remains unclear. Estrogen-induced GPER-dependent proliferation was assessed in the immortalized nontumorigenic human breast epithelial cell line, MCF10A, and an ex vivo organ culture model employing human breast tissue from reduction mammoplasty or tumor resections. Stimulation by estrogen and the GPER-selective agonist G-1 increased the mitotic index in MCF10A cells and proportion of cells in the cell cycle in human breast and breast cancer explants, suggesting increased proliferation. Inhibition of candidate signaling pathways that may link GPER activation to proliferation revealed a dependence on Src, epidermal growth factor receptor transactivation by heparin-bound EGF and subsequent ERK phosphorylation. Proliferation was not dependent on matrix metalloproteinase cleavage of membrane-bound pro-HB-EGF. The contribution of GPER to estrogen-induced proliferation in MCF10A cells and breast tissue was confirmed by the ability of GPER-selective antagonist G36 to abrogate estrogen- and G-1-induced proliferation, and the ability of siRNA knockdown of GPER to reduce estrogen- and G-1-induced proliferation in MCF10A cells. This is the first study to demonstrate GPER-dependent proliferation in primary normal and malignant human tissue, revealing a role for GPER in estrogen-induced breast physiology and pathology.
Topics: Breast; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Epithelial Cells; Estradiol; Extracellular Signal-Regulated MAP Kinases; Female; Humans; Mitotic Index; Phosphorylation; Receptors, Estrogen; Receptors, G-Protein-Coupled; Signal Transduction; Transcriptional Activation
PubMed: 24718936
DOI: 10.1007/s12672-014-0174-1 -
Journal of Clinical Pathology Jan 1994To verify the correlation between MIB-1, Ki67, and proliferating cell nuclear antigen (PCNA-PC10) scores and S-phase fraction in intermediate grade non-Hodgkin's...
AIMS
To verify the correlation between MIB-1, Ki67, and proliferating cell nuclear antigen (PCNA-PC10) scores and S-phase fraction in intermediate grade non-Hodgkin's lymphomas (Working Formulation F); and their reliability in differently processed tissues.
METHODS
Forty one non-Hodgkin's lymphomas were classified as (F) intermediate grade malignant lymphomas according to the Working Formulation; mitotic counts and percentage of large cells were assessed for each case. Sections from formalin fixed, paraffin wax embedded tissues were stained with anti MIB-1 monoclonal antibody, after microwave oven processing, and anti-PCNA (PC10) monoclonal antibody using an avidin-biotin immunoperoxidase (ABC) method. One thousand cells from 10 representative fields were scored. Frozen sections from surgical specimens were stained with Ki67 monoclonal antibody using the ABC method; the fraction of Ki67 positive cells was calculated scoring 1000 cells. Flow cytometry analysis (FCM) was performed on cell suspensions from fresh tissues. Correlations between data were estimated using linear regression.
RESULTS
A linear correlation was found between MIB-1 and Ki67 scores (r = 0.92; p < 0.00001); between MIB-1 and PCNA scores (r = 0.79; p < 0.00001); and between MIB-1 score and S-phase fraction (r = 0.51; p = 0.0006). A linear correlation was also found between Ki67 and PCNA scores (r = 0.85; p < 0.00001); between Ki67 score and S-phase fraction (r = 0.6; p = 0.0002); and between PCNA score and S-phase fraction (r = 0.74; p < 0.00001). A correlation was found between mitotic counts and MIB-1 (r = 0.56; p = 0.0001), PCNA (r = 0.51; p = 0.0007), or Ki67 scores (r = 0.47; p = 0.002); between the percentage of large cells and MIB-1 (r = 0.49; p = 0.0009), PCNA (r = 0.6; p = 0.00003), and Ki67 scores (r = 0.53; p = 0.0003) and S-phase fraction (r = 0.55; p = 0.0002).
CONCLUSION
MIB-1, Ki67, and PCNA (PC10) scores and S-phase fraction are highly correlated and equally well represent the proliferative activity of intermediate grade non-Hodgkin's lymphomas in differently processed material. MIB-1 and PCNA stains can be applied even on small biopsy specimens. MIB-1 produces homogenous staining without background; it also strongly stains mitotic figures. It can be performed on routinely processed tissues, permitting the simultaneous evaluation of the morphology and tumour cell kinetics. The wide standard deviations of the proliferative indices found for intermediate grade NHL suggest that this category probably includes various degrees of malignancy.
Topics: Antibodies, Monoclonal; Antigens, Neoplasm; DNA, Neoplasm; Female; Flow Cytometry; Humans; Immunoenzyme Techniques; Ki-67 Antigen; Lymphoma, Non-Hodgkin; Male; Middle Aged; Mitotic Index; Neoplasm Proteins; Nuclear Proteins; Proliferating Cell Nuclear Antigen; S Phase
PubMed: 7907607
DOI: 10.1136/jcp.47.1.18 -
Oncotarget Jul 2017Background Due to the extremely rare incidence, data of clinicopathological features and prognosis of mesenteric gastrointestinal stromal tumors (GISTs) are limited....
Background Due to the extremely rare incidence, data of clinicopathological features and prognosis of mesenteric gastrointestinal stromal tumors (GISTs) are limited. Therefore, the aim of the present study was to investigate the clinicopathological features and prognosis of mesenteric GISTs.Patients and Methods Mesenteric GISTs cases were obtained from our center and from case reports and clinical series extracted from MEDLINE. Clinicopathological features and survivals were analyzed.Results A total of 114 mesenteric GISTs were enrolled in present study. The most common symptom was abdominal pain (20/72, 27.8%), followed by abdominal mass (13/72, 18.1%) and distention (9/72, 12.5%). Most tumors exceeded 10 cm in diameter (71/112, 63.4%), exceeded 5/50HPF in mitotic index (50/85, 58.8%), and were high risk (82/90, 91.1%). The five-year disease free survival (DFS) and disease specific survival (DSS) was 57.7% and 60.1%, respectively. Tumor size and mitotic index were associated with DFS and DSS. The distribution of tumor size, histological type, mitotic index and NIH risk category were significantly different between mesenteric and gastric GISTs. Prognosis of mesenteric GISTs was worse than that of gastric GISTs. However, multivariate analysis showed that location was not an independent prognostic factor for mesenteric and gastric GISTs.Conclusions Most mesenteric GISTs exceeded 10 cm in diameter, exceeded 5/50HPF in mitotic index and were high risk. Mesenteric GISTs differed significantly from gastric GISTs in respect to clinicopathologic features. Mitotic index and tumor size were prognostic factors for mesenteric GISTs. The prognosis were comparable between mesenteric and gastric GISTs.
Topics: Adult; Aged; Biomarkers, Tumor; Female; Gastrointestinal Stromal Tumors; Humans; Male; Mesentery; Middle Aged; Mitotic Index; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Survival Analysis; Tumor Burden
PubMed: 28147326
DOI: 10.18632/oncotarget.14880 -
World Journal of Gastroenterology Oct 2022Gastrointestinal stromal tumors (GISTs) with a diameter of < 2 cm are called small GISTs. Currently, endoscopic ultrasound (EUS) is widely used as a regular follow-up...
BACKGROUND
Gastrointestinal stromal tumors (GISTs) with a diameter of < 2 cm are called small GISTs. Currently, endoscopic ultrasound (EUS) is widely used as a regular follow-up method for GISTs, which can also provide a preliminary basis for judging the malignancy potential of lesions. However, there are no studies on the accuracy of EUS to assess the malignant potential of small GISTs.
AIM
To evaluate the efficacy of EUS in the diagnosis and risk assessment of small GISTs.
METHODS
We collected data from patients with small GISTs who were admitted to Shengjing Hospital of China Medical University between October 2014 and July 2019. The accurate diagnosis and risk classifications of patients were based on the pathological assessment according to the modified National Institute of Health criteria after endoscopic resection or laparoscopic surgery. Preoperative EUS features (marginal irregularity, cystic changes, homogeneity, ulceration, and strong echogenic foci) were retrospectively analyzed. The assessment results based on EUS features were compared with the pathological features.
RESULTS
A total of 256 patients (69 men and 187 women) were enrolled. Pathological results included 232, 16, 7, and 1 very low-, low-, intermediate-, and high-risk cases, respectively. The most frequent tumor location was the gastric fundus (78.1%), and mitoses were calculated as > 5/50 high power field in 8 (3.1%) patients. Marginal irregularity, ulceration, strong echo foci, and heterogeneity were detected in 1 (0.4%), 2 (0.8%), 22 (8.6%), and 67 (65.1%) patients, respectively. However, cystic changes were not detected. Tumor size was positively correlated with the mitotic index ( < 0.001). Receiver operating curve analysis identified 1.48 cm as the best cut-off value to predict malignant potential (95% confidence interval: 0.824-0.956). EUS heterogeneity with tumor diameters > 1.48 cm was associated with higher risk classification ( < 0.05).
CONCLUSION
Small GISTs (diameters > 1.48 cm) with positive EUS features should receive intensive surveillance or undergo endoscopic surgery. EUS and dissection are efficient diagnostic and therapeutic approaches for small GISTs.
Topics: Male; Humans; Female; Gastrointestinal Stromal Tumors; Retrospective Studies; Stomach Neoplasms; Endosonography; Mitotic Index
PubMed: 36312832
DOI: 10.3748/wjg.v28.i37.5457 -
Turkish Neurosurgery 2020To evaluate the interobserver variability in determining the number of mitoses in 10 high-power field (HPF) and thus the tumor grade, and to investigate how to reduce...
AIM
To evaluate the interobserver variability in determining the number of mitoses in 10 high-power field (HPF) and thus the tumor grade, and to investigate how to reduce grade discordance between the observers and the most useful method to identify the patients who would receive an additional treatment.
MATERIAL AND METHODS
Two hundred and seventy cases with meningioma were re-evaluated by three experienced pathologists and five senior residents. They determined the number of mitotic figures in 10 HPF in each slide. Re-evaluation of the cases, which were found of different grades from the reference observers was requested by full scan method. Statistical analysis was performed by using SPSS V23.0.
RESULTS
A moderate agreement was found between the observers and the reference observer. After the evaluation of mitotic activity with the full scan method, the mean numbers of mitoses found by the observers in 10 HPF were increased. In the first evaluation, 4?6 cases were defined as Grade II by the observers. Whereas, 23?27 cases were defined as Grade II after the full scan method.
CONCLUSION
If there are less than 16 mitotic figures throughout the slide, it is more difficult to find the 10 HPF including 4 or more mitosis. Interobserver variability in mitotic figure counting can be reduced by full scan method, and examining the hematoxylin and eosin stained slides by the full scan method helps us to determine the true histologic grade of meningiomas in most cases, who would receive an additional treatment.
Topics: Humans; Meningeal Neoplasms; Meningioma; Mitotic Index; Neoplasm Grading; Observer Variation
PubMed: 32020568
DOI: 10.5137/1019-5149.JTN.26252-19.2 -
Cellular Oncology : the Official... 2007Vasculogenic mimicry, as previously described in aggressive melanoma, is characterized by the de novo generation of intratumoral patterned vascular channels, composed of...
INTRODUCTION
Vasculogenic mimicry, as previously described in aggressive melanoma, is characterized by the de novo generation of intratumoral patterned vascular channels, composed of PAS-positive basement membrane in the absence of endothelial cells, providing additional microcirculation, in support to the classic tumoral angiogenesis.
METHODS
We investigated the immunohistochemical expression of two endothelial markers, CD31 and CD34, in tumoral cells of 60 melanomas (45 primary cutaneous and 15 metastatic) as possible evidence of vasculogenic mimicry. In addition we investigated the relationship between CD31 and CD34 expression and three pathological markers such as Clark's level, and skin ulceration, predictive of melanoma's aggressive behaviour, and mitotic index.
RESULTS
No cases of common melanocytic nevi immunoreacted with CD31 or CD34. Random CD31 immunoreactivity was present in 6% of Clark's level I/II, 50% of Clark's level III and 80% Clark's level IV/V. CD34 was negative in Clark's level I/II but randomly stained the 20% and 55% of level III and IV/V respectively. 66% (10/15) of metastatic melanomas were CD31 positive showing a canalicular immunostaining pattern, conversely CD34 expression was never found. 7/8 cutaneous ulcerated melanomas immunostained for CD31 and 4/8 for CD34. CD31 immunostained 88% high/intermediate MI, and 53% of low MI melanomas. CD34 decorated the 29% of high/intermediate and 38% of low MI melanomas.
CONCLUSIONS
CD31 and CD34 immunoreactivity closely parallel both the different morphologic steps of melanocytic tumor progression and the presence of histological parameters related to the aggressive behaviour. Their expression could be related to endothelial transdifferentiation of melanoma cells although a consequent functional role has not been demonstrated yet.
Topics: Antigens, CD34; Biomarkers, Tumor; Cell Differentiation; Endothelial Cells; Humans; Immunohistochemistry; Melanoma; Mitotic Index; Neoplasm Metastasis; Nevus, Pigmented; Platelet Endothelial Cell Adhesion Molecule-1; Skin Neoplasms; Skin Ulcer
PubMed: 17429142
DOI: 10.1155/2007/486579 -
World Journal of Gastroenterology Sep 2021Multiple gastrointestinal stromal tumors (MGISTs) are specific and rare. Little is known about the impact of MGISTs on the survival of patients with gastrointestinal...
Clinicopathological characteristics and longterm survival of patients with synchronous multiple primary gastrointestinal stromal tumors: A propensity score matching analysis.
BACKGROUND
Multiple gastrointestinal stromal tumors (MGISTs) are specific and rare. Little is known about the impact of MGISTs on the survival of patients with gastrointestinal stromal tumors (GIST). The diagnosis, treatment and follow-up strategies of MGISTs is not specifically described in guidelines.
AIM
To compare the clinicopathological characteristics and prognosis of MGISTs and solitary GISTs (SGISTs).
METHODS
Patients diagnosed with primary GISTs from March 2010 to January 2020 were included. Due to the inhomogeneous distribution of several baseline characteristics and uneven MGIST and SGIST group sizes, propensity score matching was performed according to comorbidities, body mass index, tumor location, mitotic index, sex, age and American Society of Anesthesiologists score. Differences in clinicopathological characteristics and prognosis between patients with MGISTs and patients with SGISTs were compared.
RESULTS
Among the entire cohort of 983 patients, the incidence of MGISTs was 4.17%. Before matching, patients with MGISTs and those with SGISTs had disparities in body mass index, surgical approach, tumor size and mitotic index. After 1:4 ratio matching, the clinical baseline data were comparable. The 5-year progression-free survival rate was 52.17% in the MGIST group and 75.00% in the SGIST group ( = 0.031). On multivariate analysis, tumor location, tumor size, mitotic index, imatinib treatment and MGISTs (hazard ratio = 2.431, 95% confidence interval = 1.097-5.386, = 0.029) were identified as independent prognostic factors of progression-free survival. However, overall survival was similar between the SGIST and MGIST groups.
CONCLUSION
Patients with MGISTs had poorer progression-free survival than patients with SGISTs. Risk criteria and diagnostic and treatment strategies should be developed to achieve personalized precision therapy and maximize the survival benefit.
Topics: Gastrointestinal Stromal Tumors; Humans; Mitotic Index; Neoplasms, Multiple Primary; Prognosis; Propensity Score
PubMed: 34629824
DOI: 10.3748/wjg.v27.i36.6128