Interobserver Variability of Ki-67 Measurement in Breast Cancer

• Published in: Journal of pathology and translational medicine Vol. 50; no. 2; pp. 129 - 137
• Main Authors: Chung, Yul Ri, Jang, Min Hye, Park, So Yeon, Gong, Gyungyub, Jung, Woo-Hee
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society of Pathologists, Korean Society for Cytopathology 01.03.2016; The Korean Society of Pathologists and the Korean Society for Cytopathology; Korean Society of Pathologists & the Korean Society for Cytopathology; 대한병리학회
• Subjects: Automation; Breast cancer; Breast neoplasms; Cell cycle; Cell growth; Endocrine therapy; Estrogens; Gene expression; Immunoglobulins; Ki-67; Medical diagnosis; Multicenter; Observer variation; Original; Tumors; Working groups; 병리학; Ki-67; Breast neoplasms; Multicenter; Observer variation
• ISSN: 2383-7837; 2383-7845
• DOI: 10.4132/jptm.2015.12.24

As measurement of Ki-67 proliferation index is an important part of breast cancer diagnostics, we conducted a multicenter study to examine the degree of concordance in Ki-67 counting and to find factors that lead to its variability. Thirty observers from thirty different institutions reviewed Ki-67-stained slides of 20 different breast cancers on whole sections and tissue microarray (TMA) by online system. Ten of the 20 breast cancers had hot spots of Ki-67 expression. Each observer scored Ki-67 in two different ways: direct counting (average vs. hot spot method) and categorical estimation. Intraclass correlation coefficient (ICC) of Ki-67 index was calculated for comparative analysis. For direct counting, ICC of TMA was slightly higher than that of whole sections using average method (0.895 vs 0.858). The ICC of tumors with hot spots was lower than that of tumors without (0.736 vs 0.874). In tumors with hot spots, observers took an additional counting from the hot spot; the ICC of whole sections using hot spot method was still lower than that of TMA (0.737 vs 0.895). In categorical estimation, Ki-67 index showed a wide distribution in some cases. Nevertheless, in tumors with hot spots, the range of distribution in Ki-67 categories was decreased with hot spot method and in TMA platform. Interobserver variability of Ki-67 index for direct counting and categorical estimation was relatively high. Tumors with hot spots showed greater interobserver variability as opposed to those without, and restricting the measurement area yielded lower interobserver variability.