Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma.
Proliferative activity, assessed by Ki67 immunohistochemistry (IHC), is an established prognostic and predictive biomarker of breast cancer (BC). However, it remains under-utilized due to lack of standardized robust measurement methodologies and significant intratumor heterogeneity of expression. A...
| Publicado en: | Virchows Archiv: European Journal of Pathology Vol. 468; no. 4; pp. 493 - 503 |
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| Autores principales: | , , , , , , , , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Springer Nature
Apr2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=114514891&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 114514891 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 09456317 O1Z jtl: Virchows Archiv: European Journal of Pathology issn: 09456317 maglogo: N pubinfo: dt: Apr2016 vid: 468 iid: 4 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 114514891 114514891 NLM26818835 114514891 10.1007/s00428-016-1907-z NLM26818835 114514891 ppf: 493 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma. aug: au: Laurinavicius, Arvydas Plancoulaine, Benoit Rasmusson, Allan Besusparis, Justinas Augulis, Renaldas Meskauskas, Raimundas Herlin, Paulette Laurinaviciene, Aida Abdelhadi Muftah, Abir Miligy, Islam Aleskandarany, Mohammed Rakha, Emad Green, Andrew Ellis, Ian Abdelhadi Muftah, Abir A Rakha, Emad A Green, Andrew R Ellis, Ian O affil: PathImage/BioTICLA, Inserm (UMR 1199), University Caen Normandy, Cancer Center F. Baclesse, Caen France sug: subj: Image Interpretation, Computer Assisted Methods Tumor Markers, Biological Breast Neoplasms Pathology Adult Middle Age Immunohistochemistry Breast Neoplasms Mortality Aged Neoplasm Invasiveness Female Prognosis Tumor Markers, Biological Analysis Cox Proportional Hazards Model Human Adult: 19-44 years Middle Aged: 45-64 years Aged: 65+ years Female ab: Proliferative activity, assessed by Ki67 immunohistochemistry (IHC), is an established prognostic and predictive biomarker of breast cancer (BC). However, it remains under-utilized due to lack of standardized robust measurement methodologies and significant intratumor heterogeneity of expression. A recently proposed methodology for IHC biomarker assessment in whole slide images (WSI), based on systematic subsampling of tissue information extracted by digital image analysis (DIA) into hexagonal tiling arrays, enables computation of a comprehensive set of Ki67 indicators, including intratumor variability. In this study, the tiling methodology was applied to assess Ki67 expression in WSI of 152 surgically removed Ki67-stained (on full-face sections) BC specimens and to test which, if any, Ki67 indicators can predict overall survival (OS). Visual Ki67 IHC estimates and conventional clinico-pathologic parameters were also included in the study. Analysis revealed linearly independent intrinsic factors of the Ki67 IHC variance: proliferation (level of expression), disordered texture (entropy), tumor size and Nottingham Prognostic Index, bimodality, and correlation. All visual and DIA-generated indicators of the level of Ki67 expression provided significant cutoff values as single predictors of OS. However, only bimodality indicators (Ashman's D, in particular) were independent predictors of OS in the context of hormone receptor and HER2 status. From this, we conclude that spatial heterogeneity of proliferative tumor activity, measured by DIA of Ki67 IHC expression and analyzed by the hexagonal tiling approach, can serve as an independent prognostic indicator of OS in BC patients that outperforms the prognostic power of the level of proliferative activity. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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