Ki67 Evaluation in Breast Cancer: Molecular Pathology Using Digital Imaging
Kinan Drak Alsibai, Sandy Azoulay, Odile Languille-Mimoune, Bruno Poulet, Anne Barres, Camilo Adem. Institut de Pathologie de Paris, Paris, France
Background: Proliferation is of major interest in breast cancer management. Ki67 evaluation is considered as a strong surrogate marker for classifying tumors. It is widely available and its evaluation done by routine light microscopy. Proliferation markers are also included in the approved molecular chips dedicated to breast cancer. Our objective was to compare the evaluation of Ki67 by routine microscopy, with its evaluation by digital imaging using different methods (whole slide versus hotspot).
Design: Breast cancer cases were prospectively collected over a time period. Pathologists reported Ki 67 score as they did routinely according to the current recommendation (Dowsett M, JNCI 2011). After their report signed out, all slides were scanned using Ventana iScan Coreo. Digital slides were evaluated by the mean of Virtuoso (software, Ventana Roche). Two digital measurements were made, appreciation of the hostpots and then the whole slide (as if it was macrodissected for molecular technique). All values were compared and discrepancies noted.
Results: Complete date was available for 48 cases (19 biopsies, 29 surgical specimens). Since there is no consensus on the threshold for Ki67 to classify highly proliferating tumor versus low proliferating tumor, three different analyses were conducted across all three methods (routine, hotspot, whole slide); using 14% cutoff showed 14 discordant cases (29%), while using either 20% or 30% cutoff showed 6 discordant cases (14%). Comparing hotspot versus whole slide evaluation showed higher mean index for the former (20%) compared to the latter one (14%), as expected because of the stromal cells included in the whole slide analysis. Again in this latest comparison, either 20% or 30% cutoff showed only 4% discordant cases while 21% discordant cases were seen if the cutoff was set at 14%.
Conclusions: Digital imaging of whole slide might increase robustness of Ki67 evaluation in comparison with molecular high throughput technologies. As for Her2 score 2, Ki67 evaluation could have an equivocal index range, such as 1 to 30%, where further evaluation (independent interpretation by another pathologist or digital imaging) should be recommended. Combining biomarkers and standardized evaluation by immunohistochemistry in a complex mathematical algorithm (such as IHC4) could therefore help in a better management of a specific subset of breast cancer patients.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 270, Wednesday Morning