Ki 67 assessment in breast cancer in an Egyptian population: a comparative study between manual assessment on optical microscopy and digital quantitative assessment

Essam Ayad, Ahmed Soliman, Shady Elia Anis, Amira Ben Salem, Pengchao Hu, Youhong Dong

Breast cancer is by far the most frequent cancer among women. The proliferative index, Ki-67, is more and more taken into consideration for treatment decisions. However, the reliability of the established Ki-67 scoring is limited. Digital pathology is currently suggested to be a potential solution to Ki 67 assessment problems. This is a retrospective and prospective study including 100 patients diagnosed with invasive breast cancer. Three senior pathologists have been asked to estimate the Ki-67 proliferative index for each of the 100 cases by examining the whole glass slides on optical microscope and providing a continuous score then a categorical score ('high' and 'low' Ki 67 index) using once 14%, once 20% as threshold indicative of high Ki67 status. Finally, a digital quantitative assessment of Ki67 was performed. A high inter-observer agreement was found when using optical microscopy for Ki 67 assessment, with correlation coefficient (CC) estimated at 0.878 (p value < 0.01). The overall agreement between manual and automated evaluation of Ki 67 was only substantial (CC estimated at 0.745 (p value < 0.01)). When using categorical scores, the inter-observers concordance was substantial using both cutoff points with kappa value estimated at 0.796 ([0.696-0.925] while using 14% as a cut off point and at 0.766 ([0.672-0.938] while using 20% as a cutoff point (p value < 0). The inter-observers agreement was better while using 14% as cutoff point. Agreement between manual and automated assessment of Ki 67 indices using both cutoff points was only substantial (Kappa estimated at 0.623, p value < 0.01). In comparison to automated assessment of Ki 67 index, while using 14% as a cutoff point, the overall tendency of all observers was to overestimate the Ki 67 values but to underestimate the proliferation index while using 20% as a cutoff point. Automated assessment of Ki 67 value would appear to be comparable to visual Ki 67 assessment on optical microscopy. Such study would help define the role of digital pathology as a potential easy-to use tool for a robust and standardized fully automated Ki 67 scoring.