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MCM diagnostic technology - the advantages

Two members of Cytosystems scientific board – Professor Ron Laskey and Dr Nicholas Coleman – co-authored a scientific paper on “Control of DNA replication and its potential clinical exploitation”, published in February 2005 by Nature Reviews at www.nature.com/reviews/cancer

You can view a copy of this paper in pdf format here.

Relevant excerpts:

“MCMs have recently emerged as useful biomarkers of cell cycle ‘state’; that is, whether a cell is capable of proliferating, rather than being quiescent or senescent.”

“The ability of MCMs to distinguish cycling cells from quiescent cells has prompted a potential clinical application in cancer screening approaches that rely on the detection of malignant or pre-malignant cells exfoliated from surface epithelia, such as in cervical screening16. Existing biomarkers of cell-cycle entry include Ki67 and proliferating cell nuclear antigen (PCNA). These biomarkers are not as sensitive as MCMs in detecting cells that are in cycle and therefore are unlikely to be as effective in this clinical setting. MCMs are expressed throughout G1 phase, whereas Ki67 might not be expressed until late G1 phase.”

“Immunostaining for MCMs in routine cervical smears could potentially improve the current method of cervical cancer screening by cytological assessment using the Papanicolau (Pap) stain. This stain is composed of Harris’s haematoxylin, to assess nuclear morphology, and three cytoplasmic dyes (orange G, eosin Y and light green) to determine the degree of keratinocyte differentiation, and it is subjective and error-prone as an isolated test.”

“Two different technical approaches have identified MCMs as powerful predictors of clinical outcome in several epithelial malignancies. Immunohistochemical studies using MCMs as candidate markers have described a potential role for the analysis of MCM expression (thereby indicating the frequency of cell-cycle entry by tumour cells) in predicting survival in patients with breast cancer, non-small cell lung cancer, brain tumours, prostate cancer, oesophageal cancer, renal cell cancer, bladder cancer and oral squamous cell carcinoma. In selecting treatment for cervical cancer, the MCM labelling index might also prove to be of value as a predictive marker of tumours that respond to radiation therapy.”


 

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