151:. Among solid tumors, the clinical significance of the proliferation index on breast cancer has been extensively studied. Mitotic counting has also been shown in multiple studies to have prognostic value in breast cancer, where a lower count of mitotic cells correlates with a more favorable outcome, and thus has been incorporated into part of the histological grading system. The Ki-67 labelling index has also been found to have prognostic significance where in many clinical practice guidelines, evaluation of Ki-67 in newly diagnosed invasive breast carcinomas is recommended. Additionally, the tumor proliferation index has been used to predict the response to systemic chemotherapies in patients who are receiving
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number in a defined number of high power fields, such as 10 mitoses in 10 high power fields. Since the field of vision area can vary considerably between different microscopes, the exact area of the high power fields should be defined in order to compare results from different studies. Accordingly, one of the main problems of counting mitosis has been the reproducibility. Thus, the need for standardized methodology and strict protocols is important to achieve reproducible results. Automated image alalysis using deep learning-based algorithms has been proposed as a promising tool to assist pathologists and thereby improve reproducibility and accuracy.
63:
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stained with a Ki-67 antibody, and the number of stained nuclei is then expressed as a percentage of total tumor cells. It is recommended to count at least 500 tumor cells in the highest labeled area. The Ki-67 score closely correlates with other proliferation markers, and has been shown to have prognostic and predictive value for many different tumor types. Similarly,
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375:
Ann-Kathrin; Heier, Annabelle; Lehmbecker, Annika; Merz, Sophie; Noland, Erika L; Plog, Stephanie; Schmidt, Anja; Sebastian, Franziska; Sledge, Dodd G; Smedley, Rebecca C; Tecilla, Marco; Thaiwong, Tuddow; Fuchs-Baumgartinger, Andrea; Meuten, Donald J; Breininger, Katharina; Kiupel, Matti; Maier, Andreas; Klopfleisch, Robert (2021).
38:(or growth fraction) has clinical significance in characterizing many solid tumors and hematologic malignancies. This has led investigators to develop different technologies to evaluate the proliferation index in tumor samples. The most commonly used methods in evaluating a proliferative index include
748:
Groheux, David; Biard, L.; Lehmann-Che, J.; Teixeira, L.; Bouhidel, F. A.; Poirot, B.; Bertheau, P.; Merlet, P.; Espié, M. (2018-04-04). "Tumor metabolism assessed by FDG-PET/CT and tumor proliferation assessed by genomic grade index to predict response to neoadjuvant chemotherapy in triple negative
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and proliferating cell nuclear antigen is a commonly used method to determine the proliferation index. Ki-67 is a nuclear antigen expressed in proliferating cells that is coded by the MKI67 gene on chromosome 10, and is expressed during the GI, S, G2, and M phases of the cell cycle. Cells are then
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through flow cytometry provides an estimate of the fractions of cells within each of the phases in the cell cycle. Cell nuclei are stained with a DNA binding stain and the amount of staining is measured from the histogram. The fractions of cells within the different cell cycle phases (G0/G1, S and
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stained sections. It is usually expressed as the number of cells per microscopic field. Cells in the mitotic phase are identified by the typical appearance of their chromosomes in the cell during the mitotic phase of the cell cycle. Usually the number of mitotic figures is expressed as the total
374:
Bertram, Christof A; Aubreville, Marc; Donovan, Taryn A; Bartel, Alexander; Wilm, Frauke; Marzahl, Christian; Assenmacher, Charles-Antoine; Becker, Kathrin; Bennett, Mark; Corner, Sarah; Cossic, Brieuc; Denk, Daniela; Dettwiler, Martina; Gonzalez, Beatriz Garcia; Gurtner, Corinne; Haverkamp,
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van Diest, P. J.; Baak, J. P.; Matze-Cok, P.; Wisse-Brekelmans, E. C.; van Galen, C. M.; Kurver, P. H.; Bellot, S. M.; Fijnheer, J.; van Gorp, L. H. (June 1992). "Reproducibility of mitosis counting in 2,469 breast cancer specimens: results from the
Multicenter Morphometric Mammary Carcinoma
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The various methods of characterizing the proliferation index have found roles in both the diagnostic and prognostic evaluation of tumors. For instances, the number of mitotic cells is used to classify tumors. In general, a high proliferation index suggests malignancy and
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A bromodeoxyuridine assay, similar to thymidine-labeling indexing, incubates cells with radiolabeled bromodeoxyuridine, which is taken up at a greater rate by proliferating cells, and then uses a film to image the distribution of radiolabeled bromodeoxyuridine in cells.
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Wenger, C. R.; Beardslee, S.; Owens, M. A.; Pounds, G.; Oldaker, T.; Vendely, P.; Pandian, M. R.; Harrington, D.; Clark, G. M. (October 1993). "DNA ploidy, S-phase, and steroid receptors in more than 127,000 breast cancer patients".
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Elston, C. W.; Ellis, I. O. (November 1991). "Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up".
138:, which is expressed throughout the phases of the cell cycle. The expression of PCNA also correlates well with other proliferation markers such as mitotic count, S-phase fraction and Ki-67 staining.
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systemic therapy where patients who have tumors with high tumor proliferative index respond better to systemic cytotoxic therapies than those who have tumors with a low tumor proliferative index.
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Loo, Suet Kee; Ch'ng, Ewe Seng; Lawrie, Charles H.; Muruzabal, María
Arestin; Gaafar, Ayman; Pomposo, María Puente; Husin, Azlan; Salleh, Md. Salzihan Md.; Banham, Alison H. (December 2017).
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Mitotic indexing is the oldest method of assessing proliferation and is determined by counting the number of mitotic figures (cells undergoing mitosis) through a light microscope on
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and most fundamental biological processes in tumors, is associated with tumor progression, response to therapy, and cancer patient survival. Consequently, the evaluation of a tumor
134:(PCNA) is a protein associated with cell proliferation that is upregulated in proliferating cells, making it another useful antigen for immunostaining. It is associated with
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Dowsett, Mitch; Nielsen, Torsten O.; A’Hern, Roger; Bartlett, John; Coombes, R. Charles; Cuzick, Jack; Ellis, Matthew; Henry, N. Lynn; Hugh, Judith C. (2011-11-16).
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Yerushalmi, Rinat; Woods, Ryan; Ravdin, Peter M; Hayes, Malcolm M; Gelmon, Karen A (February 2010). "Ki67 in breast cancer: prognostic and predictive potential".
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Azambuja, E; Cardoso, F; Castro, G de; Colozza, M; Mano, M S; Durbecq, V; Sotiriou, C; Larsimont, D; Piccart-Gebhart, M J (May 2007).
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377:"Computer-assisted mitotic count using a deep learning–based algorithm improves interobserver reproducibility and accuracy"
250:"DNMT1 is predictive of survival and associated with Ki-67 expression in R-CHOP-treated diffuse large B-cell lymphomas"
527:"Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients"
693:"Assessment of Ki67 in Breast Cancer: Recommendations from the International Ki67 in Breast Cancer Working Group"
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sections after incubating the tumor cells with thymidine. Rapidly proliferating cells readily update more
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Silvestrini, R. (1994-10-01). "Cell kinetics: prognostic and therapeutic implications in human tumours".
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Wang, Xing; Wang, Dong; Yuan, Na; Liu, Fanxiao; Wang, Fu; Wang, Bomin; Zhou, Dongsheng (2017-10-01).
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G2/M compartments) can then be calculated from the histogram by computerized cell cycle analysis.
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The immunohistochemical detection of proliferation related proteins such as
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Thymidine, which produces darker spots on the autoradiograph film.
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entry in the public domain NCI Dictionary of Cancer Terms
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Baak, J. P. (July 1990). "Mitosis counting in tumors".
172:Hanahan, Douglas; Weinberg, Robert A. (2011).
54:evaluation of cell cycle-associated proteins.
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174:"Hallmarks of Cancer: The Next Generation"
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58:Mitotic index (also called mitotic count)
27:Index measuring the progression of cancer
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142:Diagnostic role of proliferation index
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476:Breast Cancer Research and Treatment
654:10.1111/j.1365-2559.1991.tb00229.x
444:10.1111/j.1365-2184.1994.tb01376.x
132:proliferating cell nuclear antigen
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815: This article incorporates
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828:U.S. National Cancer Institute
121:Immunohistochemical evaluation
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227:10.1016/s1470-2045(09)70262-1
30:Proliferation, as one of the
345:10.1016/0046-8177(92)90313-r
301:10.1016/0046-8177(90)90026-2
266:10.1016/j.pathol.2017.08.009
600:10.1097/md.0000000000008254
108:S-phase fraction evaluation
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823:Dictionary of Cancer Terms
191:10.1016/j.cell.2011.02.013
763:10.1007/s00259-018-3998-z
531:British Journal of Cancer
390:10.1177/03009858211067478
83:Thymidine-labeling index
99:Bromodeoxyuridine assay
817:public domain material
543:10.1038/sj.bjc.6603756
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381:Veterinary Pathology
136:DNA polymerase alpha
68:neuroendocrine tumor
804:Proliferative index
709:10.1093/jnci/djr393
215:The Lancet Oncology
52:immunohistochemical
36:proliferative index
18:Proliferation index
488:10.1007/BF00666351
432:Cell Proliferation
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16:(Redirected from
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