Introduction. Developments in immunological and quantitative real-time PCR-based analysis have enabled the detection, enumeration, and characterization of circulating tumor cells (CTCs). It is assumed that the detection of CTCs is associated with cancer, based on the finding that CTCs can be detected in all major cancer and not in healthy subjects or those with benign disease. Methods and Patients. Consecutive men, with suspicion of prostate cancer, had blood samples taken before prostate biopsy; mononuclear cells were obtained using differential gel centrifugation and CPCs detecting using anti-PSA immunocytochemistry. Positive samples underwent further classification with anti-P504S. Results. 329 men underwent prostate biopsy; of these men 83 underwent a second biopsy and 44 a third one. Of those with a biopsy negative for cancer, 19/226 (8.4%) had CPCs PSA (+) P504S (?) detected at first biopsy, 6/74 (8.1%) at second biopsy, and 5/33 (15.2%) at third biopsy. Men with cancer-positive biopsies did not have PSA (+) P504S (?) CPCs detected. These benign cells were associated with chronic prostatitis. Conclusions. Patients with chronic prostatitis may have circulating prostate cells detected in blood, which do not express the enzyme P504S and should be thought of as benign in nature. 1. Introduction Although the first report on circulating tumors was published by Ashworth in 1869 [1], the lack of technology precluded further investigations on their clinical use until recently. Developments in immunological and quantitative real-time PCR-based analysis have enabled the detection, enumeration and characterization of circulating tumor cells (CTCs). The monitoring of CTCs has the potential to improve therapeutic management at an early stage and also to identify patients with increased risk of tumor progression or recurrence before the onset of clinically detected metastasis. Furthermore, the molecular profiling of CTCs can provide new insights into cancer biology and systemic treatment in neoadjuvant or adjuvant settings. It is assumed that the detection of CTCs is associated with cancer, based on the finding that CTCs can be detected in all major cancers and not in healthy subjects or those with benign disease [2]. Most of the assays are based on enrichment and subsequent identification of CTCs using monoclonal antibodies directed against epithelial epitopes, for example, the transmembrane glycoprotein epithelial cell adhesion molecule (EpCAM) or cytokeratins that are expressed on both normal and malignant cells. This widely based approach is based on the
References
[1]
T. R. Ashworth, “A case of cancer in which cells similar to those in the tumours were seen in the blood after death,” Medical Journal of Australia, vol. 14, pp. 146–149, 1869.
[2]
W. J. Allard, J. Matera, M. C. Miller et al., “Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases,” Clinical Cancer Research, vol. 10, no. 20, pp. 6897–6904, 2004.
[3]
K. Pantel, E. Denéve, D. Nocca, et al., “Circulating epitelial cells in patients with benign colon diseases,” Clinical Chemistry, vol. 58, no. 5, pp. 936–940, 2012.
[4]
S. D. Mikolajczyk, L. S. Millar, P. Tsinberg et al., “Detection of EpCAM-negative and cytokeratin-negative circulating tumor cells in peripheral blood,” Journal of Oncology, vol. 2011, Article ID 252361, 10 pages, 2011.
[5]
M. Zhou, A. M. Chinnaiyan, C. G. Kleer, P. C. Lucas, and M. A. Rubin, “Alpha-methylacyl-CoA racemase: a novel tumor marker over-expressed in several human cancers and their precursor lesions,” American Journal of Surgical Pathology, vol. 26, no. 7, pp. 926–931, 2002.
[6]
R. Beach, A. M. Gown, M. N. De Peralta-Venturina et al., “P504S immunohistochemical detection in 405 prostatic specimens including 376 18-gauge needle biopsies,” American Journal of Surgical Pathology, vol. 26, no. 12, pp. 1588–1596, 2002.
[7]
N. P. Murray, G. M. Calaf, L. Badinez et al., “P504S expressing prostate cells as a marker for prostate cancer,” Oncology Reports, vol. 24, no. 3, pp. 689–692, 2010.
[8]
N. P. Murray, E. Reyes, P. Tapia, et al., “Diagnostic performance of malignant prostate cells detected in blood for early detection of prostate cancer: comparison to prostatic biopsy,” Archivos Espa?oles de Urología, vol. 64, no. 10, pp. 961–971, 2011.
[9]
A. Ouzzane, P. Coloby, J. P. Mignard et al., “Guidelines for prostatic biopsies best practice,” Progres en Urologie, vol. 21, no. 1, pp. 18–28, 2011.
[10]
E. Borgen, B. Naume, J. M. Nesland et al., “Standardization of the immunocytochemical detection of cancer cells in BM and blood: I. establishment of objective criteria for the evaluation of immunostained cells: the European ISHAGE working group for Standardization of Tumor Cell Detection,” Cytotherapy, vol. 1, no. 5, pp. 377–388, 1999.
[11]
M. A. Rubin, M. Zhou, S. M. Dhanasekaran et al., “Alpha-methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer,” Journal of the American Medical Association, vol. 287, no. 13, pp. 1662–1670, 2002.
[12]
L. M. Coussens and Z. Werb, “Inflammation and cancer,” Nature, vol. 420, no. 6917, pp. 860–867, 2002.
[13]
J. W. Davis, H. Nakanishi, V. S. Kumar et al., “Circulating tumor cells in peripheral blood samples from patients with increased serum prostate specific antigen: initial results in early prostate cancer,” Journal of Urology, vol. 179, no. 6, pp. 2187–2191, 2008.
[14]
P. Eschwège, S. Moutereau, S. Droupy et al., “Prognostic value of prostate circulating cells detection in prostate cancer patients: a prospective study,” British Journal of Cancer, vol. 100, no. 4, pp. 608–610, 2009.
[15]
S. L. Stott, R. J. Lee, S. Nagrath, et al., “Isolation and characterization of cir-culating tumor cell from patients with localized and metastatic prostate cancer,” Science Translational Medicine, vol. 2, no. 25, p. 25, 2010.
[16]
N. Thiounn, F. Saporta, T. A. Flam et al., “Positive prostate-specific antigen circulating cells detected by reverse transcriptase-polymerase chain reaction does not imply the presence of prostatic micrometastases,” Urology, vol. 50, no. 2, pp. 245–250, 1997.
[17]
F. A. W. Coumans, C. J. M. Doggen, G. Attard, J. S. de Bono, and L. W. M. M. Terstappen, “All circulating EpCAM+CK+CD45-objects predict overall survival in castration-resistant prostate cancer,” Annals of Oncology, vol. 21, no. 9, pp. 1851–1857, 2010.