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oai:recercat.cat:11351/64032024-12-27T07:16:14Zcom_2072_378070com_2072_378040col_2072_378092

urn:hdl:11351/6403 Sequential immunohistochemistry and virtual image reconstruction using a single slide for quantitative KI67 measurement in breast cancer Fasani, Roberta Pagliuca, Francesca Gallego Valades, Francisca Jiménez Flores, José Antonio Peg Camara, Vicente Ramon y Cajal Agüeras, Santiago Nuciforo, Paolo Giovanni Saura Manich, Cristina Serna, Garazi Guardia, Xavier Simonetti, Sara Mama - Càncer Immunohistoquímica Imatges - Processament - Tècniques digitals DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms INFORMATION SCIENCE::Information Science::Computing Methodologies::Image Processing, Computer-Assisted ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Histocytochemistry::Immunohistochemistry ENFERMEDADES::enfermedades de la piel y tejido conjuntivo::enfermedades de la piel::enfermedades de la mama::neoplasias de la mama CIENCIA DE LA INFORMACIÓN::Ciencias de la información::metodologías computacionales::procesamiento de imágenes asistido por ordenador TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::técnicas y procedimientos diagnósticos::técnicas de laboratorio clínico::técnicas citológicas::histocitoquímica::inmunohistoquímica Càncer de mama; Anàlisi d'imatges digitals; Quantificació de Ki67 Breast cancer; Digital image analysis; Ki67 quantification Cáncer de mama; Análisis de imágenes digitales; Cuantificación de Ki67 Objective Ki67 is a prognostic and predictive marker in breast cancer (BC). However, manual scoring (MS) by visual assessment suffers from high inter-observer variability which limits its clinical use. Here, we developed a new digital image analysis (DIA) workflow, named KiQuant for automated scoring of Ki67 and investigated its equivalence with standard pathologist's assessment. Methods Sequential immunohistochemistry of Ki67 and cytokeratin, for precise tumor cell recognition, were performed in the same section of 5 tissue microarrays containing 329 tumor cores from different breast cancer subtypes. Slides were digitalized and subjected to DIA and MS for Ki67 assessment. The intraclass correlation coefficient (ICC) and Bland-Altman plot were used to evaluate inter-observer reproducibility. The Kaplan-Meier analysis was used to determine the prognostic potential. Results KiQuant showed an excellent correlation with MS (ICC:0.905,95%CI:0.878–0.926) with satisfactory inter-run (ICC:0.917,95%CI:0.884–0.942) and inter-antibody reproducibilities (ICC:0.886,95%CI:0.820–0.929). The distance between KiQuant and MS increased with the magnitude of Ki67 measurement and positively correlated with analyzed tumor area and breast cancer subtype. Agreement rates between KiQuant and MS within the clinically relevant 14% and 30% cut-off points ranged from 33% to 44% with modest interobserver reproducibility below the 20% cut-off (0.606, 95%CI:0.467–0.727). High Ki67 by KiQuant correlated with worse outcome in all BC and in the luminal subtype ( P = 0.028 and P = 0.043, respectively). For MS, the association with survival was significant only in 1 out of 3 observers. Conclusions KiQuant represents an easy and accurate methodology for Ki67 measurement providing a step toward utilizing Ki67 in the clinical setting. 2021-10-18T08:18:20Z 2021-10-18T08:18:20Z 2020-10-01 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Breast;53 https://doi.org/10.1016/j.breast.2020.07.002 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Elsevier Scientia