Proliferative index: Difference between revisions

Revision as of 04:59, 21 April 2018

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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 2007/05|title=Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients|url=http://www.nature.com/articles/6603756|journal=British Journal of Cancer|language=En|volume=96|issue=10|pages=1504–1513|doi=10.1038/sj.bjc.6603756|issn=1532-1827}}</ref>. Similarly, [[proliferating cell nuclear antigen]] (PCNA) is a protein associated with cell proliferation that is upregulated in proliferating cells, making it another useful antigen for immunostaining<ref>{{Cite journal|last=Wang|first=Xing|last2=Wang|first2=Dong|last3=Yuan|first3=Na|last4=Liu|first4=Fanxiao|last5=Wang|first5=Fu|last6=Wang|first6=Bomin|last7=Zhou|first7=Dongsheng|date=2017-10-01|title=The prognostic value of PCNA expression in patients with osteosarcoma|url=http://Insights.ovid.com/crossref?an=00005792-201710130-00023|journal=Medicine|language=ENGLISH|volume=96|issue=41|doi=10.1097/md.0000000000008254|issn=0025-7974}}</ref>. It is associated with [[DNA polymerase|DNA polymerase alpha]], 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.

== 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|url=https://www.ncbi.nlm.nih.gov/pubmed/1757079|journal=Histopathology|volume=19|issue=5|pages=403–410|issn=0309-0167|pmid=1757079}}</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|url=https://academic.oup.com/jnci/article/103/22/1656/890097|journal=JNCI: Journal of the National Cancer Institute|language=en|volume=103|issue=22|pages=1656–1664|doi=10.1093/jnci/djr393|issn=0027-8874}}</ref>. Additionally, the tumor proliferation index has been used to predict the response to systemic chemotherapies in patients who are receiving [[Neoadjuvant therapy|neoadjuvant]] 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<ref>{{Cite journal|last=Groheux|first=David|last2=Biard|first2=L.|last3=Lehmann-Che|first3=J.|last4=Teixeira|first4=L.|last5=Bouhidel|first5=F. A.|last6=Poirot|first6=B.|last7=Bertheau|first7=P.|last8=Merlet|first8=P.|last9=Espié|first9=M.|date=2018-04-04|title=Tumor metabolism assessed by FDG-PET/CT and tumor proliferation assessed by genomic grade index to predict response to neoadjuvant chemotherapy in triple negative breast cancer|url=https://link.springer.com/article/10.1007/s00259-018-3998-z|journal=European Journal of Nuclear Medicine and Molecular Imaging|language=en|pages=1–10|doi=10.1007/s00259-018-3998-z|issn=1619-7070}}</ref>.

==References==

{{Reflist}}

==External links==