Andrew Dodson

dodsonStandardisation of Ki67 in breast cancer prognostication

The assessment of proliferation in normal and diseased tissues by the immunohistochemical demonstration of the presence of Ki67 protein provides important information to the cell biology researcher and clinical pathologist alike. In the context of breast pathology, its principle use is to inform on prognosis and additionally it is also useful in prediction of response to treatment [1].
The presentation will introduce some of the recent advances that have been made in understanding the precise role of Ki67 in the cell cycle and will then discuss the practicalities of its assessment with regard to reproducibility and clinical utility, and review some of the progress that has been made in standardisation [2, 3].
Ki67 is used as a stand-alone reporter of proliferation levels and is also incorporated in a variety of algorithms such as IHC4+C and the Magee Equations [4, 5]. We will look at the advantages and disadvantages of both approaches.

  1. Denkert, C., et al., Strategies for developing Ki67 as a useful biomarker in breast cancer. Breast, 2015. 24 Suppl 2: p. S67-72.

  2. Polley, M.Y., et al., An international study to increase concordance in Ki67 scoring. Mod Pathol, 2015. 28(6): p. 778-86.

  3. Dodson, A., et al., Risk of recurrence estimates with IHC4+C are tolerant of variations in staining and scoring: an analytical validity study. J Clin Pathol, 2016. 69(2): p. 128-35.

  4. Dowsett, M., et al., Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study. J Clin Oncol, 2010. 28(11): p. 1829-34.

  5. Klein, M.E., et al., Prediction of the Oncotype DX recurrence score: use of pathology-generated equations derived by linear regression analysis. Mod Pathol, 2013. 26(5): p. 658-64.

CV

I began my career as a biomedical scientist in 1981 at St George’s Hospital in London where I trained in histopathology and was first introduced to the science of immunocytochemistry. In the early 1990’s I took up a post at the Royal Liverpool University Hospital, where I managed their Immunocytochemistry laboratories for both clinical and academic services. Latterly in my time there I was increasingly involved the introduction of molecular pathology into the diagnostics services. In 1995 I became an assessor for the UK NEQAS ICC & ISH scheme and I am the scheme’s deputy director, a post I have held since 2008. In 2013 I returned to London to a post in clinical research at the Royal Marsden Hospital within the then newly established Ralph Lauren Centre for Breast Cancer Research.

Recent publications

  1. Gellert P, Segal CV, Gao Q, López-Knowles E, Martin LA, Dodson A, Li T, Miller CA, Lu C, Mardis ER, Gillman A, Morden J, Graf M, Sidhu K, Evans A, Shere M, Holcombe C, McIntosh SA, Bundred N, Skene A, Maxwell W, Robertson J, Bliss JM, Smith I, Dowsett M; POETIC Trial Management Group and Trialists. Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation. Nat Commun. 2016 Nov 9;7:13294

  2. Kirwan CC, Coles CE, Bliss J; PRIMETIME Protocol Working Group.; PRIMETIME Protocol Working Group. It’s PRIMETIME. Postoperative Avoidance of Radiotherapy: Biomarker Selection of Women at Very Low Risk of Local Recurrence. Clin Oncol (R Coll Radiol). 2016 Sep;28(9):594-6.

  3. López-Knowles E, Gao Q, Cheang MC, Morden J, Parker J, Martin LA, Pinhel I, McNeill F, Hills M, Detre S, Afentakis M, Zabaglo L, Dodson A, Skene A, Holcombe C, Robertson J, Smith I, Bliss JM, Dowsett M; POETIC trialists. Heterogeneity in global gene expression profiles between biopsy specimens taken peri-surgically from primary ER-positive breast carcinomas. Breast Cancer Res. 2016 Apr1;18(1):39.

  4. Dodson A, Zabaglo L, Yeo B, Miller K, Smith I, Dowsett M. Risk of recurrence estimates with IHC4+C are tolerant of variations in staining and scoring: an analytical validity study. J Clin Pathol. 2016 Feb;69(2):128-35.

  5. Yeo B, Zabaglo L, Hills M, Dodson A, Smith I, Dowsett M. Clinical utility of the IHC4+C score in oestrogen receptor-positive early breast cancer: a prospective decision impact study. Br J Cancer. 2015 Jul 28;113(3):390-5.