Challenging, Accurate and Feasible: CAF-1 as a Tumour Proliferation Marker of Diagnostic and Prognostic Value.

Abstract

Simple SummaryThere is an emerging need for new weapons in the battle against cancer; therefore, the discovery of new biomarkers with diagnostic, prognostic, and therapeutic value is a priority of current cancer research. An important task is to identify how quickly a tumour proliferates. A tumour’s proliferation rate is critical for grading and clinical decision-making; hence, there is an imperative need for accurate proliferation markers. Here, we review evidence demonstrating that chromatin assembly factor 1 (CAF-1) is a proliferation marker of clinical value. CAF-1 is selectively expressed in proliferating cells and its expression can be evaluated by immunohistochemistry in cytology smears and biopsies. CAF-1 expression is increased in almost all cancers and correlates strongly with the expression of Ki-67, the current routine proliferation marker. Overexpression of CAF-1 is associated with poor clinical outcome (advanced cancer stage, recurrence, metastasis, and decreased survival). CAF-1 is a robust, reproducible, and feasible proliferation marker of prognostic importance and may represent an attractive alternative or complementary to Ki-67 for cancer stratification and clinical guidance.The discovery of novel biomarkers of diagnostic, prognostic, and therapeutic value is a major challenge of current cancer research. The assessment of tumour cell proliferative capacity is pivotal for grading and clinical decision-making, highlighting the importance of proliferation markers as diagnostic and prognostic tools. Currently, the immunohistochemical analysis of Ki-67 expression levels is routinely used in clinical settings to assess tumour proliferation. Inasmuch as the function of Ki-67 is not fully understood and its evaluation lacks standardization, there is interest in chromatin regulator proteins as alternative proliferation markers of clinical value. Here, we review recent evidence demonstrating that chromatin assembly factor 1 (CAF-1), a histone chaperone selectively expressed in cycling cells, is a proliferation marker of clinical value. CAF-1 expression, when evaluated by immunocytochemistry in breast cancer cytology smears and immunohistochemistry in cancer biopsies from several tissues, strongly correlates with the expression of Ki-67 and other proliferation markers. Notably, CAF-1 expression is upregulated in almost all cancers, and CAF-1 overexpression is significantly associated, in most cancer types, with high histological tumour grade, advanced stage, recurrence, metastasis, and decreased patient survival. These findings suggest that CAF-1 is a robust, reproducible, and feasible proliferation marker of prognostic importance. CAF-1 may represent an attractive alternative or complementary to Ki-67 for cancer stratification and clinical guidance.