Cytomorphology of Circulating Colorectal Tumor Cells:A Small Case Series

Several methodologies exist to enumerate circulating tumor cells (CTCs) from the blood of cancer patients; however, most methodologies lack high-resolution imaging, and thus, little is known about the cytomorphologic features of these cells. In this study of metastatic colorectal cancer patients, we used immunofluorescent staining with fiber-optic array scanning technology to identify CTCs, with subsequent Wright-Giemsa and Papanicolau staining. The CTCs were compared to the corresponding primary and metastatic tumors. The colorectal CTCs showed marked intrapatient pleomorphism. In comparison to the corresponding tissue biopsies, cells from all sites showed similar pleomorphism, demonstrating that colorectal CTCs retain the pleomorphism present in regions of solid growth. They also often retain particular cytomorphologic features present in the patient's primary and/or metastatic tumor tissue. This study provides an initial analysis of the cytomorphologic features of circulating colon cancer cells, providing a foundation for further investigation into the significance and metastatic potential of CTCs.

[1]  H. Scher,et al.  Circulating Tumor Cell Analysis in Patients with Progressive Castration-Resistant Prostate Cancer , 2007, Clinical Cancer Research.

[2]  B. Molnár,et al.  Circulating tumor cell clusters in the peripheral blood of colorectal cancer patients. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[3]  J. Nieva,et al.  Case study of the morphologic variation of circulating tumor cells. , 2007, Human pathology.

[4]  Jonathan W. Uhr,et al.  Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases , 2004, Clinical Cancer Research.

[5]  Tanja Fehm,et al.  Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[6]  R. Moll Cytokeratins as markers of differentiation in the diagnosis of epithelial tumors. , 1998, Sub-cellular biochemistry.

[7]  Jason L. Townson,et al.  The role of apoptosis in tumor progression and metastasis. , 2003, Current molecular medicine.

[8]  Mehmet Toner,et al.  Detection of mutations in EGFR in circulating lung-cancer cells. , 2008, The New England journal of medicine.

[9]  M. Sanz-Casla,et al.  Circulating tumor cells in colorectal cancer: correlation with clinical and pathological variables. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[10]  Alison Stopeck,et al.  Circulating tumor cells, disease progression, and survival in metastatic breast cancer. , 2004, The New England journal of medicine.

[11]  Alison Stopeck,et al.  Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  R. Gangnus,et al.  Genomic Profiling of Viable and Proliferative Micrometastatic Cells from Early-Stage Breast Cancer Patients , 2004, Clinical Cancer Research.

[13]  T. Kroll,et al.  Monitoring the response of circulating epithelial tumor cells to adjuvant chemotherapy in breast cancer allows detection of patients at risk of early relapse. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  Ruud H. Brakenhoff,et al.  Detection, clinical relevance and specific biological properties of disseminating tumour cells , 2008, Nature Reviews Cancer.

[15]  S. Braun,et al.  Comparative analysis of micrometastasis to the bone marrow and lymph nodes of node-negative breast cancer patients receiving no adjuvant therapy. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[17]  J. Izbicki,et al.  Methodological analysis of immunocytochemical screening for disseminated epithelial tumor cells in bone marrow. , 1994, Journal of hematotherapy.

[18]  Rakesh K Jain,et al.  Active versus passive mechanisms in metastasis: do cancer cells crawl into vessels, or are they pushed? , 2007, The Lancet. Oncology.

[19]  Anne Vincent-Salomon,et al.  Clinical Significance of Immunocytochemical Detection of Tumor Cells Using Digital Microscopy in Peripheral Blood and Bone Marrow of Breast Cancer Patients , 2004, Clinical Cancer Research.

[20]  Michael Morse,et al.  Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  Peter Kuhn,et al.  A rare-cell detector for cancer. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[22]  L. Weiner,et al.  Isolation and characterization of circulating tumor cells in patients with metastatic colorectal cancer. , 2006, Clinical colorectal cancer.

[23]  S. Eccles,et al.  Metastasis: recent discoveries and novel treatment strategies , 2007, The Lancet.

[24]  Peter Kuhn,et al.  High speed detection of circulating tumor cells. , 2006, Biosensors & bioelectronics.

[25]  S. Digumarthy,et al.  Isolation of rare circulating tumour cells in cancer patients by microchip technology , 2007, Nature.

[26]  Brigitte Rack,et al.  Detection of Circulating Tumor Cells in Peripheral Blood of Patients with Metastatic Breast Cancer: A Validation Study of the CellSearch System , 2007, Clinical Cancer Research.

[27]  R. Eils,et al.  Genomic analysis of single cytokeratin-positive cells from bone marrow reveals early mutational events in breast cancer. , 2005, Cancer cell.