Dataset Information

Correlation between ER, PR, HER-2, and Ki-67 with the risk of bone metastases detected by bone scintigraphy in breast cancer patients: A cross sectional study.

ABSTRACT:

Background

Breast cancer is one of the most common cancers in women. About 30%-85% of breast cancers will metastasize to the bone during the course of the illness. Many studies have shown that molecular marker/subtypes can be useful in determining incidence of different and inconsistent bone metastases. This study aimed to determine the correlation of the risk of bone metastases in breast cancer based on the expression of molecular markers.

Methods

The research was conducted retrospectively by searching patients' medical record data. The target population of this study was all patients diagnosed with breast cancer who came to our tertiary hospital in the Nuclear Medicine and Molecular Imaging Department from January 2012 to December 2016.

Results

One hundred and thirty patients (n = 130) were enrolled during the study period with characteristics of sex, age, and immunohistochemical/molecular subtype examination that underwent bone scintigraphy. Mean of age was 50.2 (23-79) years. There were no significant correlations between ER, PR, and HER-2 expressions with bone metastases in breast cancer patients. Ki-67 was showed to be correlated with bone metastases in breast cancer patients in our bivariate analysis. Molecular subtype/markers had no statistically significant correlation with bone metastases in patients with breast cancer.

Conclusion

Ki-67 with high proliferation index was the most powerful molecular marker to determine the risk of bone metastases. The prevalence of bone metastases in the group with Ki-67 expression with high proliferation (≥20) was 1.8 times greater than the prevalence of bone metastases in the weakest HER-2 group.

SUBMITTER: Afkari H

PROVIDER: S-EPMC8256177 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Proliferation may predict response to neoadjuvant therapy of breast cancer and is commonly assessed by manual scoring of slides stained by immunohistochemistry (IHC) for Ki-67 similar to ER and PgR. This method carries significant intra- and inter-observer variability. Automatic scoring of Ki-67 with digital image analysis (qIHC) or assessment of MKI67 gene expression with RT-qPCR may improve diagnostic accuracy.Ki-67 IHC visual assessment was compared to the IHC nuclear tool (AperioTM) on core biopsies from a randomized neoadjuvant clinical trial. Expression of ESR1, PGR and MKI67 by RT-qPCR was performed on RNA extracted from the same formalin-fixed paraffin-embedded tissue. Concordance between the three methods (vIHC, qIHC and RT-qPCR) was assessed for all 3 markers. The potential of Ki-67 IHC and RT-qPCR to predict pathological complete response (pCR) was evaluated using ROC analysis and non-parametric Mann-Whitney Test.Correlation between methods (qIHC versus RT-qPCR) was high for ER and PgR (spearman´s r?=?0.82, p?<?0.0001 and r?=?0.86, p?<?0.0001, respectively) resulting in high levels of concordance using predefined cut-offs. When comparing qIHC of ER and PgR with RT-qPCR of ESR1 and PGR the overall agreement was 96.6 and 91.4%, respectively, while overall agreement of visual IHC with RT-qPCR was slightly lower for ER/ESR1 and PR/PGR (91.2 and 92.9%, respectively). In contrast, only a moderate correlation was observed between qIHC and RT-qPCR continuous data for Ki-67/MKI67 (Spearman's r?=?0.50, p?=?0.0001). Up to now no predictive cut-off for Ki-67 assessment by IHC has been established to predict response to neoadjuvant chemotherapy. Setting the desired sensitivity at 100%, specificity for the prediction of pCR (ypT0ypN0) was significantly higher for mRNA than for protein (68.9% vs. 22.2%). Moreover, the proliferation levels in patients achieving a pCR versus not differed significantly using MKI67 RNA expression (Mann-Whitney p?=?0.002), but not with qIHC of Ki-67 (Mann-Whitney p?=?0.097) or vIHC of Ki-67 (p?=?0.131).Digital image analysis can successfully be implemented for assessing ER, PR and Ki-67. IHC for ER and PR reveals high concordance with RT-qPCR. However, RT-qPCR displays a broader dynamic range and higher sensitivity than IHC. Moreover, correlation between Ki-67 qIHC and RT-qPCR is only moderate and RT-qPCR with MammaTyper® outperforms qIHC in predicting pCR. Both methods yield improvements to error-prone manual scoring of Ki-67. However, RT-qPCR was significantly more specific.