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{{short description|Index measuring the progression of cancer}}
Proliferation, as one of the [[Hallmarks of cancer|hallmarks]] and most fundamental biological processes in tumors,<ref>{{Cite journal|last=Hanahan|first=Douglas|last2=Weinberg|first2=Robert A.|title=Hallmarks of Cancer: The Next Generation
== Mitotic index ==
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 [[H&E stain|H&E]] 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.<ref>{{Cite journal|last=Baak|first=J. P.|date=July 1990|title=Mitosis counting in tumors|journal=Human Pathology|volume=21|issue=7|pages=683–685|issn=0046-8177|pmid=2131787|doi=10.1016/0046-8177(90)90026-2}}</ref> Usually the number of mitotic figures is expressed as the total 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.<ref>{{Cite journal|last=van Diest|first=P. J.|last2=Baak|first2=J. P.|last3=Matze-Cok|first3=P.|last4=Wisse-Brekelmans|first4=E. C.|last5=van Galen|first5=C. M.|last6=Kurver|first6=P. H.|last7=Bellot|first7=S. M.|last8=Fijnheer|first8=J.|last9=van Gorp|first9=L. H.|date=June 1992|title=Reproducibility of mitosis counting in 2,469 breast cancer specimens: results from the Multicenter Morphometric Mammary Carcinoma Project|journal=Human Pathology|volume=23|issue=6|pages=603–607|issn=0046-8177|pmid=1592381|doi=10.1016/0046-8177(92)90313-r}}</ref>
== Thymidine-labeling index ==
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== Immunohistochemical evaluation ==
The immunohistochemical detection of proliferation related proteins such as [[Ki-67 (protein)|Ki-67]] 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 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.<ref>{{Cite journal|last=de Azambuja|first=E|last2=Cardoso|first2=F|last3=Castro|first3=G de|last4=Colozza|first4=M|last5=Mano|first5=M S|last6=Durbecq|first6=V|last7=Sotiriou|first7=C|last8=Larsimont|first8=D|last9=Piccart-Gebhart|first9=M J|date=May 2007|title=Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients
== Diagnostic role of proliferation index ==
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 [[Grading (tumors)|high-grade tumors]].<ref>{{Cite journal|last=Elston|first=C. W.|last2=Ellis|first2=I. O.|date=November 1991|title=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|journal=Histopathology|volume=19|issue=5|pages=403–410|issn=0309-0167|pmid=1757079|doi=10.1111/j.1365-2559.1991.tb00229.x}}</ref> 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.<ref>{{Cite journal|last=Dowsett|first=Mitch|last2=Nielsen|first2=Torsten O.|last3=A’Hern|first3=Roger|last4=Bartlett|first4=John|last5=Coombes|first5=R. Charles|last6=Cuzick|first6=Jack|last7=Ellis|first7=Matthew|last8=Henry|first8=N. Lynn|last9=Hugh|first9=Judith C.|date=2011-11-16|title=Assessment of Ki67 in Breast Cancer: Recommendations from the International Ki67 in Breast Cancer Working Group
==References==
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