Correlation of manual semi-quantitative and automated quantitative Ki-67 proliferative index with OncotypeDX^TM recurrence score in invasive breast carcinoma

Article type: Research Article

Authors: Finkelman, Brian S.^{; a} | Meindl, Amanda^b; | LaBoy, Carissa^c | Griffin, Brannan B.^d | Narayan, Suguna P.^e | Brancamp, Rachel^d | Siziopikou, Kalliopi P.^c | Pincus, Jennifer L.^f | Blanco, Jr., Luis Z.^c;

Affiliations: [a] Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA | [b] Department of Pathology, Great Lakes Pathologists, West Allis, WI, USA | [c] Department of Pathology, Section of Breast Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA | [d] Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA | [e] Department of Pathology, University of Colorado School of Medicine, Aurora, CO, USA | [f] Department of Pathology, HCA Healthcare, Denver, CO, USA

Correspondence: [*] Corresponding author: Luis Z. Blanco, Jr, Associate Professor of Pathology, Department of Pathology, Section of Breast Pathology, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, 251 East Huron Street, Feinberg Pavilion 7-340, Chicago, Illinois 60611, USA. Tel.: +1 312 926 4436; Fax: +1 312 926 3127; E-mail: luis.blanco@northwestern.edu

Note: [†] Co-first authors.

Abstract: BACKGROUND:Ki-67 immunohistochemistry (IHC) staining is a widely used cancer proliferation assay; however, its limitations could be improved with automated scoring. The OncotypeDXTM Recurrence Score (ORS), which primarily evaluates cancer proliferation genes, is a prognostic indicator for breast cancer chemotherapy response; however, it is more expensive and slower than Ki-67. OBJECTIVE:To compare manual Ki-67 (mKi-67) with automated Ki-67 (aKi-67) algorithm results based on manually selected Ki-67 “hot spots” in breast cancer, and correlate both with ORS. METHODS:105 invasive breast carcinoma cases from 100 patients at our institution (2011–2013) with available ORS were evaluated. Concordance was assessed via Cohen’s Kappa (κ). RESULTS:57/105 cases showed agreement between mKi-67 and aKi-67 (κ 0.31, 95% CI 0.18–0.45), with 41 cases overestimated by aKi-67. Concordance was higher when estimated on the same image (κ 0.53, 95% CI 0.37–0.69). Concordance between mKi-67 score and ORS was fair (κ 0.27, 95% CI 0.11–0.42), and concordance between aKi-67 and ORS was poor (κ 0.10, 95% CI −0.03–0.23). CONCLUSIONS:These results highlight the limits of Ki-67 algorithms that use manual “hot spot” selection. Due to suboptimal concordance, Ki-67 is likely most useful as a complement to, rather than a surrogate for ORS, regardless of scoring method.

Keywords: Breast carcinoma, Ki-67, OncotypeDX, digital image analysis

DOI: 10.3233/BD-201011

Journal: Breast Disease, vol. 41, no. 1, pp. 55-65, 2022