Inter-laboratory comparison of Ki-67 proliferating index detected by visual assessment and automated digital image analysis

Article type: Research Article

Authors: Tomić, Snježana^a | Mrklić, Ivana^a; | Razumović, Jasminka Jakić^b | Jonjić, Nives^c | Šarčević, Božena^d | Blažičević, Valerija^e | Jurković, Ilija^f | Vrbičić, Branka^g | Lisica Šikic, Nataša^h | Peteh, Loredana Labinacⁱ | Lončarić, Čedna Tomasović^j | Vučić, Majda^k | Gašparov, Slavko^l | Švagelj, Dražen^m | Radiković, Sandraⁿ | Mahovne, Ivana^o

Affiliations: [a] Department of Pathology, Forensic Medicine and Cytology, University Hospital Centre Split, Croatia | [b] Department of Pathology, University Hospital Centre Zagreb, Croatia | [c] Department of Pathology, Faculty of Medicine of the University of Rijeka, Croatia | [d] Department of Pathology, Clinic for Tumors, Zagreb, Croatia | [e] Department of Pathology, University Hospital Osijek, Croatia | [f] Department of Pathology, General Hospital Dubrovnik, Croatia | [g] Department of Pathology, General Hospital Šibenik, Croatia | [h] Department of Pathology, General Hospital Zadar, Croatia | [i] Department of Pathology, General Hospital Pula, Croatia | [j] Department of Pathology, Clinical Hospital Dubrava, Zagreb, Croatia | [k] Department of Pathology, University Hospital Center “Sestre Milosrdnice”, Zagreb, Croatia | [l] Department of Pathology, Clinical Hospital Merkur, Zagreb, Croatia | [m] Department of Pathology, General Hospital Vinkovci, Croatia | [n] Department of Pathology, General Hospital Varaždin, Croatia | [o] Department of Pathology, General Hospital Slavonski Brod, Croatia

Correspondence: [*] Corresponding author: Ivana Mrklić, Department of Pathology, Forensic Medicine and Cytology, University Hospital Centre Split, Spinčićeva 1, 21000 Split, Croatia. Tel.: 0038521556512; Fax: 0038521389510; E-mail: ivana.mrklic@mefst.hr

Abstract: BACKGROUND:Proliferation rate is a major determinant of the biologic behavior of the tumor and provides information that can be used to guide treatment decisions. METHODS:This ring study included 27 pathologists from 14 Institutions, in order to assess inter-observer concordance between pathologists in Croatia. We analyzed Ki-67 proliferative index on ten randomly selected breast cancer samples comparing consistency between visual assessment using light microscopy compared to digital image analyses results from one central laboratory as a referral value. RESULTS:When we analyzed Ki-67 as numeric value high concordance rate was found between Ki-67 score visually assessed in all participating Institutions compared to referral value assessed by digital image analysis (ICC 0.76, 95% CI 0.58–0.91), and Krippendorff’s alpha was 0.79 (95% CI 0.58–1.00). Concordance was better in slides with higher Ki-67 values. When we categorized Ki-67 values according to generally accepted 20% cut-off value we noticed the lower concordance rate among participants in our study. CONCLUSION:Proliferation remains one of the most important parameters for tumor characterization helpful in making clinical decisions, but it should be used with great caution. Standardization of the Ki-67 assessment is essential and proliferating index should be expressed as exact numeric value. For patients with proliferative index near the cut-off value, other factors must be considered in making clinical decisions.

Keywords: Breast cancer, immunohistochemistry, Ki-67, proliferation index

DOI: 10.3233/BD-180341

Journal: Breast Disease, vol. 38, no. 2, pp. 73-79, 2019