Universität zu Köln

Sinn, Hans-Peter ORCID: 0000-0003-2836-6699, Schneeweiss, Andreas, Keller, Marius, Schlombs, Kornelia, Laible, Mark, Seitz, Julia, Lakis, Sotirios, Veltrup, Elke, Altevogt, Peter, Eidt, Sebastian, Wirtz, Ralph M. and Marme, Frederik (2017). Comparison of immunohistochemistry with PCR for assessment of ER, PR, and Ki-67 and prediction of pathological complete response in breast cancer. BMC Cancer, 17. LONDON: BMC. ISSN 1471-2407

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Abstract

Background: 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. Methods: 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. Results: 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). Conclusion: 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 (R) outperforms qIHC in predicting pCR. Both methods yield improvements to error-prone manual scoring of Ki-67. However, RT-qPCR was significantly more specific.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Sinn, Hans-Peter UNSPECIFIED orcid.org/0000-0003-2836-6699 UNSPECIFIED Schneeweiss, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Keller, Marius UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlombs, Kornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Laible, Mark UNSPECIFIED UNSPECIFIED UNSPECIFIED Seitz, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Lakis, Sotirios UNSPECIFIED UNSPECIFIED UNSPECIFIED Veltrup, Elke UNSPECIFIED UNSPECIFIED UNSPECIFIED Altevogt, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Eidt, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirtz, Ralph M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Marme, Frederik UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-239817
DOI:	10.1186/s12885-017-3111-1
Journal or Publication Title:	BMC Cancer
Volume:	17
Date:	2017
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1471-2407
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTERNATIONAL EXPERT CONSENSUS; ESTROGEN-RECEPTOR; PROGESTERONE-RECEPTOR; AUTOMATED ASSESSMENT; MOLECULAR SUBTYPES; PROGNOSTIC VALUE; CORE BIOPSIES; KI67; NEOADJUVANT; EXPRESSION Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23981