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Diagnostic Pathology Jul 2020The mitotic count in breast carcinoma is an important prognostic marker. Unfortunately substantial inter- and intra-laboratory variation exists when pathologists...
BACKGROUND
The mitotic count in breast carcinoma is an important prognostic marker. Unfortunately substantial inter- and intra-laboratory variation exists when pathologists manually count mitotic figures. Artificial intelligence (AI) coupled with whole slide imaging offers a potential solution to this problem. The aim of this study was to accordingly critique an AI tool developed to quantify mitotic figures in whole slide images of invasive breast ductal carcinoma.
METHODS
A representative H&E slide from 320 breast invasive ductal carcinoma cases was scanned at 40x magnification. Ten expert pathologists from two academic medical centers labeled mitotic figures in whole slide images to train and validate an AI algorithm to detect and count mitoses. Thereafter, 24 readers of varying expertise were asked to count mitotic figures with and without AI support in 140 high-power fields derived from a separate dataset. Their accuracy and efficiency of performing these tasks were calculated and statistical comparisons performed.
RESULTS
For each experience level the accuracy, precision and sensitivity of counting mitoses by users improved with AI support. There were 21 readers (87.5%) that identified more mitoses using AI support and 13 reviewers (54.2%) that decreased the quantity of falsely flagged mitoses with AI. More time was spent on this task for most participants when not provided with AI support. AI assistance resulted in an overall time savings of 27.8%.
CONCLUSIONS
This study demonstrates that pathology end-users were more accurate and efficient at quantifying mitotic figures in digital images of invasive breast carcinoma with the aid of AI. Higher inter-pathologist agreement with AI assistance suggests that such algorithms can also help standardize practice. Not surprisingly, there is much enthusiasm in pathology regarding the prospect of using AI in routine practice to perform mundane tasks such as counting mitoses.
Topics: Breast Neoplasms; Carcinoma, Ductal, Breast; Deep Learning; Female; Humans; Image Processing, Computer-Assisted; Mitotic Index
PubMed: 32622359
DOI: 10.1186/s13000-020-00995-z -
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 -
Asian Pacific Journal of Cancer... 2015Gemcitabine is an anti-cancer drug with clinically uses in the treatment of various neoplasms, including breast, ovarian, non-small cell lung, pancreaticand cervical...
Gemcitabine is an anti-cancer drug with clinically uses in the treatment of various neoplasms, including breast, ovarian, non-small cell lung, pancreaticand cervical cancers, T-cell malignancies, germ cell tumours, and hepatocellular carcinomas. However, it has also been reported to have many adverse effects. Naturally occurring anti-mutagenic effects, especially those of plant origin, have recently become a subject of intensive research. The present study was therefore designed to investigate the anti-mutagenic effects of Salvia merjamie (Family: Lamiaceae) plant extracts against the mutagenic effects of gemcitabine. The anti-mutagenic properties of Salvia merjamie were tested in Inbred SWR/J male and female mice bone marrow cells. The mice were treated in four groups; a control group treated with 30 mg/kg body weight gemcitabine and three treatment groups, each with 30 mg/kg body weight gemcitabine together with, respectively, 50, 100 and 150 mg/kg body weight Salvia merjamie extract. Chromosomal aberration and mitotic index assays were performed with the results demonstrating that Salvia merjamie extract protects bone marrow cells in mice against gemcitabine induced mutagenicity. This information can be used for the development of a potential therapeutic anti-mutagenic agents.
Topics: Animals; Antimetabolites, Antineoplastic; Antimutagenic Agents; Bone Marrow; Camphanes; Cells, Cultured; Chromosome Aberrations; Deoxycytidine; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Female; Male; Mice; Mitosis; Mitotic Index; Panax notoginseng; Salvia miltiorrhiza; Gemcitabine
PubMed: 25743821
DOI: 10.7314/apjcp.2015.16.4.1501 -
Anais Da Academia Brasileira de Ciencias 2017Tricyclazole is currently one of the fungicides recommended for the treatment of diseases in irrigated rice. However, there is relatively little information on its...
Tricyclazole is currently one of the fungicides recommended for the treatment of diseases in irrigated rice. However, there is relatively little information on its cytotoxic and genotoxic potential. The objective of this study was to evaluate the cytotoxicity and genotoxicity of rice crop water after apllication of the tricyclazole fungicide through the Allium cepa L. test. The rice crop water samplings were collected before and 1, 15 and 30 days after application of the fungicide in rice plant shoots. The Allium cepa roots were placed in contact with the rice crop water to check for possible chromosomal abnormalities and mitotic index of the bioindicators meristematic cells. The data obtained by the Allium cepa test indicates that the application of the tricyclazole fungicide leads to an increase in the genotoxic activity in the rice crop water, through the appearance of chromosomal abnormalities, without, however, causing significant effects on the mitotic index. The major chromosomal alterations observed were anaphasic and telophasic bridges and laggard chromosomes.
Topics: Agricultural Irrigation; Chromosome Aberrations; Crops, Agricultural; DNA Damage; Fungicides, Industrial; Mitosis; Mitotic Index; Mutagenicity Tests; Onions; Oryza; Thiazoles; Water Pollutants, Chemical
PubMed: 28489188
DOI: 10.1590/0001-3765201720150536 -
The American Journal of Surgical... Jun 2013The prognostic value of mitotic rate in melanoma is increasingly recognized, particularly in thin melanoma in which the presence or absence of a single mitosis/mm can...
The prognostic value of mitotic rate in melanoma is increasingly recognized, particularly in thin melanoma in which the presence or absence of a single mitosis/mm can change staging from T1a to T1b. Still, accurate mitotic rate calculation (mitoses/mm) on hematoxylin and eosin (H&E)-stained sections can be challenging. Antimonoclonal mitotic protein-2 (MPM-2) and antiphosphohistone-H3 (PHH3) are 2 antibodies reported to be more mitosis-specific than other markers of proliferation such as Ki-67. We used light microscopy and computer-assisted image analysis software to quantify MPM-2 and PHH3 staining in melanoma. We then compared mitotic rates by each method with conventional H&E-based mitotic rate for correlation with clinical outcomes. Our study included primary tissues from 190 nonconsecutive cutaneous melanoma patients who were prospectively enrolled at New York University Langone Medical Center with information on age, gender, and primary tumor characteristics. The mitotic rate was quantified manually by light microscopy of corresponding H&E-stained, MPM-2-stained, and PHH3-stained sections. Computer-assisted image analysis was then used to quantify immunolabeled mitoses on the previously examined PHH3 and MPM-2 slides. We then analyzed the association between mitotic rate and both progression-free and melanoma-specific survival. Univariate analysis of PHH3 found significant correlation between increased PHH3 mitotic rate and decreased progression-free survival (P=0.04). Computer-assisted image analysis enhanced the correlation of PHH3 mitotic rate with progression-free survival (P=0.02). Regardless of the detection method, neither MPM-2 nor PHH3 offered significant advantage over conventional H&E determination of mitotic rate.
Topics: Adult; Biomarkers, Tumor; Disease-Free Survival; Female; Humans; Image Interpretation, Computer-Assisted; Immunohistochemistry; Kaplan-Meier Estimate; Male; Melanoma; Middle Aged; Mitotic Index; Neoplasm Staging; Proportional Hazards Models; Skin Neoplasms
PubMed: 23629443
DOI: 10.1097/PAS.0b013e31827e50fa -
Asian Pacific Journal of Cancer... Jul 2021One of the most reliable and decisive histologic parameters with negative prognostic impact is tumor proliferation capacity . Quantification of mitosis in H&E stained...
OBJECTIVE
One of the most reliable and decisive histologic parameters with negative prognostic impact is tumor proliferation capacity . Quantification of mitosis in H&E stained slides could be problematic and is limited by poor reproducibility and lack of objectivity. This study was designed to evaluate inter-observer variability in mitotic count using Phosphohistone H3(PHH3).
METHODS
Totally, 60 specimens with histologic diagnosis of meningioma were selected including 50 grade I, 7 grdae II and 3 grade III tumors. Mitotic figures were counted both in H&E stained sections and slides prepared by immunohistochemistry using Anti-Phosphohistone H3 Anti body by three observers with various level of expertise, independently.
RESULTS
Mean mitotic count by PHH3 method was higher than H&E staining for all three observers. Observer 1 and 2 revealed good correlation in mitotic count using H&E method, while observer 3 showed disagreement with both of them. However, all of them had good correlation in mitotic count using PHH3 method (cc=0.956,0.947,0.909).
CONCLUSION
Based on our findings, PHH3 revealed good agreement between pathologists with various level of expertise and has the capability for further contribution in meningioma grading classification and specially could be beneficial for less experienced pathologists.
Topics: Female; Histones; Humans; Male; Meningeal Neoplasms; Meningioma; Mitotic Index; Neoplasm Grading; Observer Variation; Prognosis
PubMed: 34319026
DOI: 10.31557/APJCP.2021.22.7.2049 -
BMC Veterinary Research Apr 2017Ki67 index, tumor associated macrophages (TAMs) and mast cells (MCs) are associated with malignancies in animal and human neoplasms including colorectal carcinomas...
BACKGROUND
Ki67 index, tumor associated macrophages (TAMs) and mast cells (MCs) are associated with malignancies in animal and human neoplasms including colorectal carcinomas (CRC). This has not been assessed in canine CRC. Given similar genetic abnormalities between human and canine CRC, we assessed Ki-67 and mitotic indices, TAMs and MC count (MCC) in canine CRC (n = 17). TAMs and MCC were compared with those in adenomas (n = 13) and control (n = 9).
RESULTS
Ki-67 index in CRC (17.13 ± 11.50) was strongly correlated (r = 0.98, p < 0.05) with mitotic index (3.52 ± 1.80). MCC was higher (p < 0.05) in CRC (6.30 ± 3.98) than in adenomas (0.78 ± 0.77) and control (0.35 ± 0.33). The results suggest that Ki-67 index and MCC are associated with malignancy in canine CRC. Higher average TAMs were counted in adenomas (21.30 ± 20.70) and in CRC (11.00 ± 9.82) than in the control (7.69 ± 7.26), although the differences were not significant (p > 0.05).
CONCLUSION
Ki-67 index, TAMs and MCC in canine CRC were recorded for the first time in this study. Ki-67 index and MCC are associated with malignancy in canine CRC. Quantitative assessment of MCs and Ki-67 coupled with mitotic index and other clinical parameters may help in evaluating malignancy in canine CRC. TAMs likely play a role in the development of canine colorectal tumors. Further studies to determine the clinical significance of these parameters for prognostic, chemo-preventive and chemotherapeutic purposes in canine colorectal tumors are recommended.
Topics: Adenoma; Animals; Carcinoma; Colorectal Neoplasms; Dog Diseases; Dogs; Ki-67 Antigen; Macrophages; Mast Cells; Mitotic Index
PubMed: 28427401
DOI: 10.1186/s12917-017-1030-7 -
Laboratory Investigation; a Journal of... Mar 2017The construction of tissue microarrays (TMAs) with cores from a large number of paraffin-embedded tissues (donors) into a single paraffin block (recipient) is an...
The construction of tissue microarrays (TMAs) with cores from a large number of paraffin-embedded tissues (donors) into a single paraffin block (recipient) is an effective method of analyzing samples from many patient specimens simultaneously. For the TMA to be successful, the cores within it must capture the correct histologic areas from the donor blocks (technical accuracy) and maintain concordance with the tissue of origin (analytical accuracy). This can be particularly challenging for tissues with small histological features such as small islands of carcinoma in situ (CIS), thin layers of normal urothelial lining of the bladder, or cancers that exhibit intratumor heterogeneity. In an effort to create a comprehensive TMA of a bladder cancer patient cohort that accurately represents the tumor heterogeneity and captures the small features of normal and CIS, we determined how core size (0.6 vs 1.0 mm) impacted the technical and analytical accuracy of the TMA. The larger 1.0 mm core exhibited better technical accuracy for all tissue types at 80.9% (normal), 94.2% (tumor), and 71.4% (CIS) compared with 58.6%, 85.9%, and 63.8% for 0.6 mm cores. Although the 1.0 mm core provided better tissue capture, increasing the number of replicates from two to three allowed with the 0.6 mm core compensated for this reduced technical accuracy. However, quantitative image analysis of proliferation using both Ki67+ immunofluorescence counts and manual mitotic counts demonstrated that the 1.0 mm core size also exhibited significantly greater analytical accuracy (P=0.004 and 0.035, respectively, r=0.979 and 0.669, respectively). Ultimately, our findings demonstrate that capturing two or more 1.0 mm cores for TMA construction provides superior technical and analytical accuracy over the smaller 0.6 mm cores, especially for tissues harboring small histological features or substantial heterogeneity.
Topics: Cell Proliferation; Fluorescent Antibody Technique; Humans; Ki-67 Antigen; Mitotic Index; Paraffin Embedding; Pilot Projects; Reproducibility of Results; Tissue Array Analysis; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 28112755
DOI: 10.1038/labinvest.2016.151 -
Acta Cirurgica Brasileira Jun 2012To analyse histopathological alterations characterized by the mitotic index in the mucosa of the large intestine in Wistar rats submitted to jejunoileal bypass operation...
PURPOSE
To analyse histopathological alterations characterized by the mitotic index in the mucosa of the large intestine in Wistar rats submitted to jejunoileal bypass operation after continued administration of sodium nitrite and vitamin C to different groups.
METHODS
Eighty male Wistar rats were employed and separated into 12 groups. In the control group (20 rats): five animals ingested only water; five animals received vitamin C; five animals received sodium nitrite and five received sodium nitrite + vitamin C. In the sham group (20 rats), the animals were anesthetized and underwent midline laparotomy and only intestinal manipulation was performed: five animals ingested only water; five animals received vitamin C; five animals received sodium nitrite and five received sodium nitrite + vitamin C. In the operated group 40 rats underwent a jejunoileal bypass surgery: ten animals ingested only water; ten animals received vitamin C; ten animals received sodium nitrite and ten received sodium nitrite + vitamin C. The mean weight of the animals was measured weekly. The large intestine was subdivided into cecum (S1), ascending colon (S(2)), transverse colon (S(3)), descending colon (S(4)) and rectum (S(5)) for histopathological analysis and mitotic counts. The statistical analysis was used to compare the mitotic indices. The level of significance was 5%.
RESULTS
The mean of all the segments indicates that the sodium nitrite+vitamin C group obtained the lowest mitotic index compared to the other treatments in the control group. The segments S(1) and S(2) showed a statistical difference with the vitamin C treatment: a higher mitotic index and better preservation of the mucosa in the operated group. In the sham group the main statistical difference occurred only in the sodium nitrite+vitamin C group between the means of the segments.
CONCLUSIONS
The comparison of all the colonic segments of the various groups revealed a lower mitotic index in the animals treated with sodium nitrite+vitamin C. In addition, it was found that vitamin C did not present a statistically significant inhibiting effect on the preservation of the mucosa and the mitotic index.
Topics: Animals; Antioxidants; Ascorbic Acid; Food Preservatives; Intestinal Mucosa; Intestine, Large; Jejunoileal Bypass; Male; Mitosis; Mitotic Index; Rats; Rats, Wistar; Sodium Nitrite
PubMed: 22666752
DOI: 10.1590/s0102-86502012000600002 -
Genetics and Molecular Research : GMR Dec 2005Rotenone is a heterocyclic compound widely used as an insecticide, acaricide and piscicide. Its toxicity is mainly caused by the inhibition of mitochondrial respiratory...
Rotenone is a heterocyclic compound widely used as an insecticide, acaricide and piscicide. Its toxicity is mainly caused by the inhibition of mitochondrial respiratory processes and ATP production, resulting in the generation of reactive oxygen species. Reactive oxygen species can interact with DNA, RNA and proteins, leading to cell damage, followed by death. We used the Comet assay, and we analyzed chromosome aberrations, in order to evaluate the genotoxic and clastogenic effects of rotenone on the different phases of the cell cycle. Cultured human lymphocytes were treated with 1.0, 1.5 and 2.0 microg/mL rotenone during the G1, G1/S, S (pulses of 1 and 6 h), and G2 phases of the cell cycle. Rotenone induced DNA damage and was clastogenic, but the clastogenicity was detected only with treatments conducted during the G1/S and S phases of the cell cycle. Rotenone also induced endoreduplication and polyploidy in treatments made during G1, while it significantly reduced the mitotic index in all phases of the cell cycle.
Topics: Adult; Cell Cycle; Cells, Cultured; Chromosome Aberrations; Comet Assay; DNA Damage; Female; Humans; Insecticides; Lymphocytes; Male; Mitotic Index; Rotenone
PubMed: 16475130
DOI: No ID Found