Laboratory validation studies in Ki-67 digital image analysis of breast carcinoma: a pathway to routine quality assurance

Morgan Wang, Sally Mclaren, Roopaa Jeyathevan, Benjamin Michael Allanson, Amanda Ireland, Alexandra Kang, Katie Meehan, Carla Thomas, Cleo Robinson, Marais Combrinck, Jennet Harvey, Greg Sterrett, Benjamin Dessauvagie

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5 Citations (Scopus)


Ki-67 proliferative index (PI) has prognostic and predictive value in invasive breast carcinoma (IBC), but clinical uptake has been hampered by suboptimal accuracy, reproducibility and standardisation. Published guidelines have addressed pre-analytical and analytical factors to improve Ki-67 PI utility; however, practicalities of ongoing monitoring of Ki-67 PI quality in IBC reporting have not been established. We aimed to evaluate the internal and external quality of our established digital Ki-67 PI IBC reporting practice at a tertiary institution.

In the 5 years since initial validation work, we've completed a series of internal and external quality assurance (QA) projects: (1) an interobserver agreement study, (2) a two site interlaboratory agreement study, (3) determination of the error of our Ki-67 results, (4) an audit of the year-toyear Ki-67 values, (5) an audit of Ki-67 in neoadjuvant chemotherapy (NAC) treated cases, and (6) comparison of our Ki-67 datasets with similar published datasets.

There was excellent concordance (intra-class correlation = 0.98) and good agreement [kappa (k) = 0.76-0.96] between pathologists, excellent concordance [Pearson correlation (R) = 0.94] and very good agreement (k = 0.80) between laboratories and excellent concordance (R = 0.92-0.95) and good agreement (k = 0.67-1.0) over time for our Ki-67 results. No significant difference was observed in Ki-67 data from year-to-year. Expected associations with clinico-pathological prognosticators, pathological complete response following NAC and mitotic index were evident. The median Ki-67 values from the overall and NAC treated datasets were within the range reported in other studies, and our data could be separated into similarly proportioned 'high' and 'low' Ki-67 PI groups when dichotomised as per protocols in other studies.

Collectively, our work provides evidence of adequate internal and external quality control for our digital Ki-67 PI IBC reporting protocols. Given the paucity of formal Ki-67 QA programs, our approach could be emulated, and results compared between laboratories as a framework for internal and external Ki-67 QA.

Original languageEnglish
Pages (from-to)246-252
Number of pages7
Issue number3
Publication statusPublished - Apr 2019


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