Low concordance of biomarkers in histopathological and cytological material from breast cancer

Stålhammar, Gustav; Rosin, Gustaf; Fredriksson, Irma; Bergh, Jonas; Hartman, Johan

doi:10.1111/his.12344

Cited by 17 publications

(31 citation statements)

References 63 publications

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“…Importantly, in this study, ER assessments by cytology and consecutive tumour resections showed high concordance (96.5%–98.5%). However, previous results from our laboratory have shown 9% discordance between ICC and IHC-assessed ER using the same cut-off ≥1% 12. This discrepancy could be explained by a smaller sample size in the previous study (eligible patients for ER comparison n=133).…”

Section: Discussionmentioning

confidence: 62%

“…This dual analysis provides a unique opportunity to investigate and compare the diagnostic efficacy of both methods. Related to this, we have previously shown that Ki67 and other predictive biomarkers differ in preoperative fine-needle aspiration cytology compared with resected primary breast tumours 12. The aims of the present study were to investigate the concordance of consecutive biomarker assessment in invasive breast tumours performed on preoperative fine-needle aspiration cytology using ICC and on the tumour resection specimen using IHC, and to investigate concordance with molecular subtype and outcome with both methods.…”

Section: Introductionmentioning

confidence: 80%

“…Variation in cut-offs for ‘high’ and ‘low’ Ki67 and the lack of an optimal cut-off are an established issue concerning Ki67 6 17. As described in an earlier paper from our group, local adjustment to optimise Ki67 cut-off is one way to improve discrimination of luminal A versus B tumours 12. In Sweden, we are now implementing a guideline with a Ki67-intermediate subgroup.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic value of Ki67 analysed by cytology or histology in primary breast cancer

et al. 2018

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AimsThe accuracy of biomarker assessment in breast pathology is vital for therapy decisions. The therapy predictive and prognostic biomarkers oestrogen receptor (ER), progesterone receptor, HER2 and Ki67 may act as surrogates to gene expression profiling of breast cancer. The aims of this study were to investigate the concordance of consecutive biomarker assessment by immunocytochemistry on preoperative fine-needle aspiration cytology versus immunohistochemistry (IHC) on the corresponding resected breast tumours. Further, to investigate the concordance with molecular subtype and correlation to stage and outcome.MethodsTwo retrospective cohorts comprising 385 breast tumours with clinicopathological data including gene expression-based subtype and up to 10-year overall survival data were evaluated.ResultsIn both cohorts, we identified a substantial variation in Ki67 index between cytology and histology and a switch between low and high proliferation within the same tumour in 121/360 cases. ER evaluations were discordant in only 1.5% of the tumours. From cohort 2, gene expression data with PAM50 subtype were used to correlate surrogate subtypes. IHC-based surrogate classification could identify the correct molecular subtype in 60% and 64% of patients by cytology (n=63) and surgical resections (n=73), respectively. Furthermore, high Ki67 in surgical resections but not in cytology was associated with poor overall survival and higher probability for axillary lymph node metastasis.ConclusionsThis study shows considerable differences in the prognostic value of Ki67 but not ER in breast cancer depending on the diagnostic method. Furthermore, our findings show that both methods are insufficient in predicting true molecular subtypes.

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Section: Discussionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

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Prognostic value of Ki67 analysed by cytology or histology in primary breast cancer

et al. 2018

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“…However, mitotic rate is only modestly reproducible between different observers, and varies according to sampling technique, cold ischaemia time, tissue fixation procedures, and the pathologists' time pressure and adherence to guidelines . In addition, Ki67 suffers from interlaboratory discordance, variable prognostic power, and variance in analytical practice, including a lack of standardisation regarding what tumour region to score and what cutoff to apply for high versus low proliferation . In fact, consensus guidelines are considered to be unreliable outside individual laboratories' own reference data …”

Section: Introductionmentioning

confidence: 99%

Digital image analysis of Ki67 in hot spots is superior to both manual Ki67 and mitotic counts in breast cancer

et al. 2018

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“…Unfortunately, assessments of biomarker status struggle with intra-and interobserver variability, as well as discordance with the gene expression tests. 11,12 This is perhaps especially evident for Ki67 [13][14][15] as there is no consensus on what tumor region or number of cells to score 13,16,17 and what cutoff values for the proportion of positive cells (Ki67 index) distinguish highly from lowly proliferative tumors. In fact, even the consensus guidelines that do exist have been considered unreliable outside individual laboratories' own reference data.…”

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confidence: 99%

Digital image analysis outperforms manual biomarker assessment in breast cancer

Stålhammar

Martínez

Lippert³

et al. 2016

Modern Pathology

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In the spectrum of breast cancers, categorization according to the four gene expression-based subtypes 'Luminal A,' 'Luminal B,' 'HER2-enriched,' and 'Basal-like' is the method of choice for prognostic and predictive value. As gene expression assays are not yet universally available, routine immunohistochemical stains act as surrogate markers for these subtypes. Thus, congruence of surrogate markers and gene expression tests is of utmost importance. In this study, 3 cohorts of primary breast cancer specimens (total n = 436) with up to 28 years of survival data were scored for Ki67, ER, PR, and HER2 status manually and by digital image analysis (DIA). The results were then compared for sensitivity and specificity for the Luminal B subtype, concordance to PAM50 assays in subtype classification and prognostic power. The DIA system used was the Visiopharm Integrator System. DIA outperformed manual scoring in terms of sensitivity and specificity for the Luminal B subtype, widely considered the most challenging distinction in surrogate subclassification, and produced slightly better concordance and Cohen's κ agreement with PAM50 gene expression assays. Manual biomarker scores and DIA essentially matched each other for Cox regression hazard ratios for all-cause mortality. When the Nottingham combined histologic grade (Elston-Ellis) was used as a prognostic surrogate, stronger Spearman's rank-order correlations were produced by DIA. Prognostic value of Ki67 scores in terms of likelihood ratio χ 2 (LR χ 2 ) was higher for DIA that also added significantly more prognostic information to the manual scores (LR− Δχ 2 ). In conclusion, the system for DIA evaluated here was in most aspects a superior alternative to manual biomarker scoring. It also has the potential to reduce time consumption for pathologists, as many of the steps in the workflow are either automatic or feasible to manage without pathological expertise.

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Low concordance of biomarkers in histopathological and cytological material from breast cancer

Cited by 17 publications

References 63 publications

Prognostic value of Ki67 analysed by cytology or histology in primary breast cancer

Prognostic value of Ki67 analysed by cytology or histology in primary breast cancer

Digital image analysis of Ki67 in hot spots is superior to both manual Ki67 and mitotic counts in breast cancer

Digital image analysis outperforms manual biomarker assessment in breast cancer

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