Risk of recurrence estimates with IHC4+C are tolerant of variations in staining and scoring: An analytical validity study Academic Article uri icon


  • The IHC4+C score combines assessment of oestrogen receptor (ER), progesterone receptor (PgR), HER2 and Ki67 with clinicopathological parameters to identify the risk of distant disease recurrence in patients with breast cancer, so, aiding treatment decision-making on adjuvant chemotherapy. Despite low cost and wide availability, the reported use of IHC4+C remains limited; one explanation for this is the perception that immunohistochemistry (IHC)-based methods and assessment of them lack precision, reproducibility and portability. We examined the effects of decentralised testing and easily reproducible estimate-based scoring methods on IHC4+C scores to determine its suitability for wider adoption.Sections from a breast cancer tissue micro-array (TMA) were distributed to three centres undertaking diagnostic breast cancer IHC. Centres stained sections using their standard procedures, and returned them for central assessment. The results were compared with those obtained at IHC4+C's originating hospital (Royal Marsden Hospital (RMH)). In parallel, TMA sections stained at RMH were scored by a variety of simplified non-counting-based methods. The results were compared with those produced using counting.There was a high degree of correlation between individual IHC results produced by external centres and those of RMH (r: 0.797-0.982), and between risk of distant recurrence scores derived from them (r: 0.972-0.984). Scoring methods for ER and PgR could be adapted to require less precision without significantly affecting correlation with counted results (r: 0.933 and 0.980, respectively), but correlation between estimating and counting for Ki67 was poorer (r: 0.855).IHC4+C is tolerant of variation in staining and scoring methods. Although additional confirmatory comparative studies are required, these data support use of IHC4+C in clinical practice outside RMH.


  • Dodson, A
  • Zabaglo, L
  • Yeo, Belinda
  • Miller, K
  • Smith, I
  • Dowsett, M

publication date

  • 2016

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