Clinical validation of Ki67 by quantitative reverse transcription-polymerase chain reaction (RT-PCR) in HR+/HER2- early breast cancer

Objective: To evaluate the clinical value of Ki67 by RT-PCR, we investigated the concordance of Ki67 expression by IHC and by RT-PCR, and assessed their prognostic value in HR+/HER2- early breast cancer. Methods: 1259 HR+/HER2- early breast cancer patients treated at Ruijin Hospital with recurrence score were retrospectively recruited. RT-PCR assay measurement of Ki67 was conducted by 21-gene expression assay and compared with IHC measurement of Ki67 using chi-square tests. X-tile program was used to determine the optimal cutoff point for Ki67 by RT-PCR. Survival analyses were performed by Kaplan-Meier analysis and log-rank tests, and hazard ratios were derived from the Cox proportional hazards model. Results: Ki67 by RT-PCR had a weak positive correlation with Ki67 by IHC. Pathology, grade and Ki67 expression by IHC were significantly related to the concordance between two assays, and most discordance cases were seen in patients with Ki67 ranging from 10 to 29. The estimated 3-year DFS was 96.0% in low, and 92.5% in high expression group of Ki67 by IHC, 97.0% in low and 90.4% in high expression group of Ki67 by RT-PCR. Univariate and multivariate analysis in the whole population indicated that only Ki67 by RT-PCR—but not intrinsic subtype or recurrence score—was an independent factor for DFS. Conclusions: Ki67 assessed by RT-PCR assay was weakly correlated to Ki67 by IHC. Using 5.68 as cutoff point, Ki67 by RT-PCR had shown potential as a prognostic biomarker in HR+/HER2- early breast cancer.