Low correlation between Ki67 assessed by qRT-PCR in Oncotype Dx score and Ki67 assessed by Immunohistochemistry

Abstract

Breast cancers expressing high levels of Ki67 are associated with poor outcomes. Oncotype DX test was designed for ER+/HER2− early-stage breast cancers to help adjuvant chemotherapy decision by providing a Recurrent Score (RS). RS measures the expression of 21 specific genes from tumor tissue, including Ki67. The primary aim of this study was to assess the agreement between Ki67RNA obtained with Oncotype DX RS and Ki67IHC. Other objectives were to analyze the association between the event free survival (EFS) and the expression level of Ki67RNA; and association between RS and Ki67RNA. Herein, we report a low agreement of 0.288 by Pearson correlation coefficient test between Ki67IHC and Ki67RNA in a cohort of 98 patients with early ER+/HER2− breast cancers. Moreover, Ki67RNAhigh tumors were significantly associated with the occurrence of events (p = 0.03). On the other hand, we did not find any association between Ki67IHC and EFS (p = 0.26). We observed a low agreement between expression level of Ki67RNA and Ki67 protein labelling by IHC. Unlike Ki67IHC and independently of the RS, Ki67RNA could have a prognostic value. It would be interesting to better assess the prognosis and predictive value of Ki67RNA measured by qRT-PCR. The Ki67RNA in medical routine could be a good support in countries where Oncotype DX is not accessible.

Association Between Ki-67 Proliferative Index and Oncotype-Dx Recurrence Score in Hormone Receptor-Positive, HER2-Negative Early Breast Cancers. A Systematic Review of the Literature

“…As expected, 7 studies 10 , 13 , 14 , 16 , 17 , 25 from 2011 through 2018 used the old cutoffs, that is, ODx score of ⩽18 for low risk, 18 to 30 for intermediate risk, and ⩾31 for high risk. Two studies from 2022, 27 , 28 also used the older cutoffs, likely because their patient cohorts were taken from before 2018. Six 18 , 19 , 23 , 26 , 29 , 31 studies used the new cutoffs which categorize <15 as low risk, 16 to 25 as intermediate risk, and ⩾26 as high risk, while 3 studies 20 , 21 , 24 used both criteria for their analyses.…”

“… 20 , 21 Eight studies used the modified St Gallen criteria of <20% as low and ⩾20 as high. 10 , 16 , 18 , 22 - 24 , 26 , 27 One study used 15 as the cut off albeit without any justification, 14 whereas another determined their own institutional cutoffs (⩽24 for low) based on their patient population. 28 Two studies also used <10 and >25 as cutoffs for low and high Ki-67, respectively.…”

“…One study also indicated a discrepancy between the expression of Ki-67 RNA levels and the level of Ki-67 Immunohisto Chemistry (IHC) staining. 27 It identified low agreement between results using 2 different techniques of Ki-67 reporting. On univariate analysis, Ki-67 tumor RNA levels had a higher hazard ratio of event-free survival as compared to the Ki-67 assessment via the IHC method among their patients; also, the Ki-67 RNA was better correlated to ODx RS statistically, suggesting Ki-67 reporting via qRT-PCR is a better surrogate option to ODx RS when compared to Ki-67 reporting using conventional methods.…”

“…A major discrepancy in the studies we reviewed was the variation in risk stratification cutoffs for the Ki-67 index. 10 , 14 , 16 , 18 , 20 , 24 , 26 - 29 , 31 Some articles classified Ki-67 of less than 10 as low risk, whereas others used 20 or even 15 as a cutoff. Variations in these cutoffs may be due to changes in the standard criteria over time, for example, St Gallen updated their cutoff for Ki-67 from less than 14% to 20% to differentiate between the luminal-A and luminal-B subtypes based on survival outcomes.…”

Prognostic values of clinical and molecular features in HER2 low-breast cancer with hormonal receptor overexpression: features of HER2-low breast cancer

“…Interestingly, protein expression of Ki-67 showed prognostic value in HER2-low patients, while mRNA level of Ki-67 did not. The results difficult to reproduce and lack of consensus on Ki-67 threshold might undermine the reliability of the prognostic value of protein expression of Ki-67 [24][25][26]. Therefore, proliferationrelated multi-genes might reflect the proliferation ability of tumors better than protein expression of Ki-67 alone.…”