Ki67 and proliferation in breast cancer

Abstract

New approaches to the prognostic assessment of breast cancer have come from molecular profiling studies. A major feature of this work has been to emphasise the importance of cancer cell proliferation as a key discriminative indicator of recurrence risk for oestrogen receptor positive breast cancer in particular. Mitotic count scoring, as a component of histopathological grade, has long formed part of a routine evaluation of breast cancer biology. However, there is an increasingly compelling case to include a specific proliferation score in breast cancer pathology reports based on expression of the cell cycle regulated protein Ki67. Immunohistochemical staining for Ki67 is a widely available and economical test with good tolerance of pre-analytical variations and staining conditions. However, there is currently no evidence based protocol established to derive a reliable and informative Ki67 score for routine clinical use. In this circumstance, pathologists must establish a standardised framework for scoring Ki67 and communicating results to a multidisciplinary team.

Correlation between Ki67 and Histological Grade in Breast Cancer Patients Treated with Preoperative Chemotherapy

“…Tumors "Luminal A" (more endocrine-sensitive, indolent and with better prognosis) and "Luminal B" (less endocrine-sensitive and aggressive) can be distinguished by their gene expression and IHC (Goldhirsch et al, 2013;Shim et al, 2014). An algorithm based on semiquantitative evaluation of the ER, PR, HER2 expression and Ki67 value (called 'IHC-4' score) has shown similar results to those achieved by genetic risk models on ER positive BC (Yoo et al, 2012;Pathmanathan and Balleine, 2013).…”

“…Knowledge of BC heterogeneity has also enabled personalize the treatment, thus BC subtype (Goldhirsch et al, 2011) affects the prognosis of the disease, and the possibility of response to endocrine therapy (ET) and CT. Intrinsic subtypes defined initially through genetic-molecular studies, are associated with certain subtypes characterized by classic histopathological parameters (Paik et al, 2004;Cuzick et al, 2011;Goldhirsch et al, 2011;Tang et al, 2011;The Cancer Genome Atlas Research Network 2012) and defined as: Luminal: phenotypically characterized by ER expression; HER2 positive: showing HER2 over expression without ER expression and TN: negative for ER, PR and HER2 (Goldhirsch et al, 2011;Reis-Filho et al, 2011). Ki67 is a nuclear protein, expressed by proliferating cells in late G1, S and G2 / M cell cycle phases; reflecting the proportion of proliferating cells and has been used as a predictor of response to ET and in recent studies, to CT. Ki67 expression, as determined by IHC, also allows to subdivide the Luminal subtype in A and B (Pathmanathan et al, 2013) (Table 1). The lack of standardization of the technique, interpretation and associated costs, do not make this a routine test in the BC pathology reports worldwide.…”

Phox2B correlates with MYCN and is a prognostic marker for neuroblastoma development

“…Immunohistochemical staining was performed for two independent proliferation markers, BrdU (26) and Ki67 (27). As Fig.…”

23. Inclusion of KI67 significantly improves performance of the predict prognostication and prediction model for early breast cancer

“…The AUC is the probability that the predicted mortality from a randomly selected patient who died will be higher than the predicted mortality from a randomly selected survivor. Comparison between v2 and v3 was made using the method of DeLong [16].…”

“…There appears little doubt that KI67 has great potential as a prognostic and predictive factor in early breast cancer [13], but integration into routine clinical management has to date been hampered by a failure to identify the optimal approach for its incorporation into prognostic tools [14][15][16]. This study was not intended to inform the current debate on finding the optimal threshold for KI67 positivity or to promote the value of KI67 as a prognostic marker.…”