Is the Ki-67 labelling index ready for clinical use?

editorial Is the Ki-67 labelling index ready for clinical use? Cancer is one of the leading causes of death worldwide. Identification of biomarkers that can detect cancer early, monitor disease progression or serve as a surrogate marker for prognosis and prediction will enable us to personalise medicine and improve care of cancer patients. Up to now, the leading parameters that define treatment recommendations in early breast cancer are estrogen receptor (ER), progesterone receptor, and human epidermal growth factor status. In the last years, global gene expression analysis studies have demonstrated the prime role of proliferation signatures in breast cancer prognosis and prediction of response to therapy [1–3]. This could also be shown in a recent meta-analysis of publicly available BC gene expression studies that revealed that the key biological drivers in nine prognostic signatures were proliferation-related genes, in addition to ER signalling and Her2/neu amplification [4]. Using the information provided by expression data, commercially available multigene assays like the Oncotype DX gene test were developed in which 5 of the 16 genes, used in the text, reflect the proliferative status of the tumour. These specific genes, which include Ki-67, are heavily weighted in the formula used to calculate the test's recurrence score [5]. Two large randomised studies, one led by the Eastern Cooperative Oncology Group called Tailorx study and the MINDACT (microarray in node negative disease may avoid chemotherapy) trial coordinated by the Breast International Group, are assessing the role of different multigene assays in determining the benefit of chemotherapy in addition to endocrine treatment in node-negative hormone-positive tumours. The panel of the St Gallen International Expert Consensus on the primary therapy of early breast cancer recommends the use of proliferation markers (e.g. Ki-67 index and mitosis) and multigene assays when choosing the appropriate systemic treatment in addition to traditional parameters, such as stage, grade, and endocrine status [6]. A search on the Web site of the American Society of Clinical Oncology revealed that the guidelines for use of biological markers in breast cancer do not include Ki-67 in the list of required routine markers [7]. The Ki-67 antigen was originally identified by a German group [8] in the early 1980s, by use of a mouse mAb against a nuclear antigen from a Hodgkin's lymphoma-derived cell line. This non-histone protein was named after the researchers' location, Ki for Kiel University, Germany, with the 67 label referring to the clone number …