© Borgis - Postępy Nauk Medycznych 4/2012, s. 343-346
Tomasz Drewa1, 2, Jan Adamowicz2, *Piotr L. Chłosta1, 3, 4
Krążące komórki nowotworowe guzów litych – klucz do nowej klasyfikacji stopnia zaawansowania raków układu moczowo-płciowego
Circulating tumour cells of solid tumours – a key to the novel clinical staging of genito-urinary neoplasms
1Department of Urology, Holy Cross Cancer Centre Kielce
Head of the Dept.: Prof. Piotr L. Chłosta, MD, PhD
2Department of Tissue Engeneering Collegium Medicum Nicolaus Copernicus University, Bydgoszcz
Head of the Dept.: Prof. Tomasz Drewa, MD, PhD
3Department of Urology, Medical Centre of Postgraduate Education Warsaw
Head of the Dept.: Prof. Andrzej Borówka, MD, PhD
4Department of Health Science, Jan Kochanowski University, Kielce
Opracowanie zawiera współczesne poglądy na temat oznaczania liczby krążących we krwi komórek nowotworowych (CTC) u chorych na raka nerkowokomórkowego, jako potencjalnego narzędzia diagnostycznego, które pozwoli na dokładniejszą ocenę stopnia zawansowania choroby i monitorowania efektów leczenia. Stosując obecne metody diagnostyczne nie potrafimy wyodrębnić grupy pacjentów szczególnie narażonych na wystąpienie przerzutów. Oznaczanie liczby krążących we krwi pacjentów CTC może stać przydatnym narzędziem diagnostycznym, które pozwoli na dokładniejszą ocenę stopnia zawansowanie choroby i monitorowanie efektów leczenia. Bardzo kusząca jest wizja wprowadzenia do diagnostyki przesiewowej i oceny skuteczności leczenia Liquid biopsy, która pozwala na szybkie wykrycie nowotworu na podstawie badania krwi.
This is a current review on the circulating tumour cells (CTC) in patients with renal cell carcinoma as a potential diagnostic tool that will allow for more accurate assessment of advanced disease and the monitoring of treatment effects. Using current diagnostic methods, we are still unable to identify patients especially prone to metastases. Assaying for levels of CTC may become a useful diagnostic tool, which will help to assess disease stage with more accuracy as well as monitor treatment outcomes. The introduction of “liquid biopsy”, for screening and treatment monitoring, forms a very attractive outlook, where cases could be easily found by a blood test.
Circulating Tumour Cells (CTC) are a population of cells that have detached from the tumour mass and are able to disseminate via the vascular system and create metastatic foci in the body (1). Initially, the immune system eliminates the circulating cancer cells from the bloodstream, but over time, the cells remain there for longer periods and become identifiable. The first published report of circulating tumour cells dates back to 1869 (2).
Prospective studies have demonstrated the effectiveness of identifying and quantifying CTCs in the prediction of malignant tumour treatment outcomes, including cancers of the breast, colon and prostate (3). Currently, intensive research is conducted on the importance of CTC in the biology and therapy of renal cell carcinoma (RCC) and transitional cell carcinoma (TCC). CTCs can be isolated from patients’ blood in the course of most cancers due to the ease of identification of the epithelial phenotype of the cancer. The presence of such cells in the blood coexists with micrometastases, which are clinically silent, and/or precedes the clinical emergence of metastases (4). CTCs are suspected of being instrumental for dissemination of the cancer during surgery, which involves mechanical manipulation and traumatisation of the primary tumour (5).
The circulating cells acquire properties of mesechymal cells, i.e. they are able to function independently. This is known as Epithelial to Mesenchymal Transition (EMT) (6). As a result of changes in their adhesion molecules, the cells separate from the primary cell population and gain the ability to migrate independently within the extracellular matrix and, eventually, outside it (7). The reverse process, known as Mesenchymal to Epithelial Transition (MET), is one of the most important stages of the development of cancer metastases. Armstrong et al. demonstrated that 80% of circulating cells of prostate or breast cancer express mesenchymal and epithelial markers (8). The authors suggested that the ratio of these markers could be a valuable prognostic parameter.
Circulating cancer cells are gradually gaining importance in clinical medicine. Many studies have especially been published on the subject of prostate cancer, where authors underscore the potential role of CTC in the prediction of survival and treatment outcomes. The presence of CTC in the patient’s bloodstream is consistent with disease that is refractory to a given treatment, which therefore requires modification (9). It has been demonstrated in an animal model that approximately 10 CT cells are sufficient to develop a new tumour in the case of renal or prostate cancer (10). Identifying CTC may in future help to discern patients who, according to standard diagnostic methods, are not qualified to undergo further radical treatment due to unfavourable prognosis regarding cure (11).
The isolation and identification of CTC is a challenge for the biotechnological industry. The main issue remains the small number of cells available for study. Normally, blood is drawn in samples of 5 to 10 ml. In a majority of cancers, the available methods are able to identify no less than 10 CTC in 1 ml of blood (12). These data regard cut-off thresholds, hence they cast doubt on experimentally applied norms. Moreover, current diagnostic methods do not allow for identification of CTCs in frozen or preserved blood. This excludes potential retrospective studies, which would certainly accelerate the wide introduction of CTC-based assays into clinical practice.
CellSearch is currently the only system with FDA (Food and Drug Administration, USA) approval for use in determining the number of circulating cancer cells (13). Nonetheless, many new devices for isolating CTC have been presented. Clinical trials are under way to assess the effectiveness of electric biosensors used to rapidly identify CTC in a small volume of blood (14,15). Progress in the isolation and identification of CTC, as well as the understanding of the value of CTC in the prevention and treatment of solid tumours, may in future allow for a “liquid biopsy”, which would identify CTC in the patient’s blood sample and help to plan individualised treatment (16).
The number of identified CTC in prostate cancer patients may in the near future become a valuable parameter used to assess the disease stage and improve treatment outcomes. In a clinical study, Stott et al. demonstrated that on average approximately 100 CTCs were found in patients with prostate cancer. The number of CTC fell in all patients on the first day following radical prostatectomy (17).
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