Immunohistochemical Ki67 after short-term hormone therapy identifies low-risk breast cancers as reliably as genomic markers

Abstract

BackgroundThe purpose of this study was to test whether immunohistochemical (IHC) Ki67 levels after short-term preoperative hormone therapy (post-Ki67) predict similar numbers of patients with favorable prognoses as genomic markers.ResultsThirty paired cases (60 samples) were enrolled in this study. Post-Ki67 levels were significantly lower than pre-treatment Ki67 levels (P < 0.001). Post-Ki67 predicted more low-risk cases (83.3%, 25/30) than pre-genomic surrogate signature(GSS) (66.7%: 20/30), but the difference in predictive power was not significant (P = 0.233). Proliferation (MKI67, STK15, Survivin, CCNB1, and MYBL2) and estrogen (ER, PGR, BCL2, and SCUBE2) related signatures were significantly downregulated after therapy (P < 0.001 and 0.041, respectively).Materials and MethodsCore needle biopsy specimens of primary breast cancer were collected at Okayama University Hospital from hormone receptor-positive and human epidermal growth factor 2-negative patients that subsequently received two weeks of neoadjuvant hormone therapy. Paired post-treatment specimens from surgical samples were also collected. IHC Ki67 levels and GSS were compared between pre- and post-hormone treatment samples. Changes of gene expression pattern in short-term hormone therapy were also assessed.ConclusionsIHC based post-Ki67 levels may have distinct predictive power compared with the naïve IHC Ki67. Future studies with larger cohorts and longer follow-up periods may be needed to validate our results.

The clinicopathological significance of UBE2C in breast cancer: a study based on immunohistochemistry, microarray and RNA-sequencing data

“…As for p53, strong nuclear staining in at least 10% of the tumor cells was regarded as positive [ 20 ]. A positive result for ER and PR staining was defined as positive nuclear reactivity in at least 1% tumor cells [ 21 ]. Negative and positive Ki-67 immunostaining corresponded to < 14% and ≥ 14% of the Ki-67 positive tumor cells, respectively [ 22 ].…”

Analytical validation of a standardised scoring protocol for Ki67 immunohistochemistry on breast cancer excision whole sections: an international multicentre collaboration

“…For example, presurgical Ki67 has been shown to be a marker for recurrence‐free survival and, in the neoadjuvant setting, a marker for endocrine‐resistant tumour that may require more aggressive treatment . Excellent intra ‐ observer reproducibility under controlled pre‐analytical and staining conditions has contributed to the body of evidence showing the potential of Ki67 immunohistochemistry assay to be implemented in hospital laboratories as a cost‐effective part of clinical management . However, poor interobserver reproducibility and variability due to technical aspects of the assay has limited its adoption in clinical practice …”

“…20 Excellent intra-observer reproducibility under controlled pre-analytical and staining conditions 21 has contributed to the body of evidence showing the potential of Ki67 immunohistochemistry assay to be implemented in hospital laboratories as a cost-effective part of clinical management. [22][23][24] However, poor interobserver reproducibility and variability due to technical aspects of the assay has limited its adoption in clinical practice. 4,9,[25][26][27][28] The International Ki67 Working Group (IKWG) has undertaken a systematic multiphase programme to determine whether Ki67 scoring can be standardised and analytically validated throughout laboratories.…”

Integration of Ki-67 index into AJCC 2018 staging provides additional prognostic information in breast tumours candidate for genomic profiling

“…Actually, Oncotype DX® is based, among others, on the expression of 5 genes related to proliferation (namely MKI67, STK15, Survivin, CCNB1 and MYBL2), and the association between both RS and single gene expression with the Ki67 IHC levels has previously been addressed. [20][21][22][23] Since use of Oncotype DX® in routine practice requires important financial resources and its cost-effectiveness has been questioned in the literature, 24,25 especially for low-risk BC patients, Ki67-PS can possibly provide additional information with an inferior burden on National Health System budget.…”