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Prognostic value of Ki67 analysed by cytology or histology in primary breast cancer
  1. Stephanie Robertson1,2,
  2. Gustav Stålhammar1,3,
  3. Eva Darai-Ramqvist2,
  4. Mattias Rantalainen4,
  5. Nicholas P Tobin1,
  6. Jonas Bergh1,5,
  7. Johan Hartman1,2,6
  1. 1 Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
  2. 2 Department of Clinical Pathology and Cytology, Karolinska University Laboratory, Stockholm, Sweden
  3. 3 St Erik Eye Hospital, Stockholm, Sweden
  4. 4 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  5. 5 Department of Radiumhemmet–Karolinska Oncology, Karolinska University Hospital, Stockholm, Sweden
  6. 6 Stockholm South General Hospital, Stockholm, Sweden
  1. Correspondence to Dr Johan Hartman, Department of Oncology and Pathology, Karolinska Institutet, SE-17176 Stockholm, Sweden ; johan.hartman{at}


Aims The 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.

Methods Two retrospective cohorts comprising 385 breast tumours with clinicopathological data including gene expression-based subtype and up to 10-year overall survival data were evaluated.

Results In 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.

Conclusions This 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.

  • breast cancer
  • Ki67
  • immunocytochemistry
  • immunohistochemistry

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  • Handling editor Dhirendra Govender.

  • Contributors SR contributed to study concept and design, data acquisition, interpretation and statistical analyses, and drafting the manuscript. GS contributed to study concept and design, data interpretation and statistical analyses, and drafting the manuscript. EDR contributed to pathological re-evaluations of tissue samples and critically reviewed the manuscript. MR provided gene expression subtype data and contributed to preparation of the manuscript and critically reviewed the manuscript. NPT and JB contributed to preparation of the manuscript and critically reviewed the manuscript. JH contributed to study concept and design, supervision of the study, data interpretation, preparation of the manuscript, and critically reviewed the manuscript. All authors have read and approved the final manuscript.

  • Funding This work was supported with grants from Swedish Society for Medical Research (SSMF), Swedish Cancer Society, Stockholm Cancer Society, King Gustaf V Jubilee Fund, Karolinska Institutet, Stockholm County Council Research Strategy Committee and Swedish Breast Cancer Association (BRO).

  • Competing interests JH is a member of the advisory board at Visiopharm, and has obtained speaker’s bureau and honoraria from Roche. Other authors have no competing interests to declare.

  • Patient consent Not required.

  • Ethics approval Regional Ethical Review Board at Karolinska Institutet.

  • Provenance and peer review Not commissioned; externally peer reviewed.