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Subclassification of prostate cancer circulating tumor cells by nuclear size reveals very small nuclear circulating tumor cells in patients with visceral metastases.

Publication ,  Journal Article
Chen, J-F; Ho, H; Lichterman, J; Lu, Y-T; Zhang, Y; Garcia, MA; Chen, S-F; Liang, A-J; Hodara, E; Zhau, HE; Hou, S; Ahmed, RS; Luthringer, DJ ...
Published in: Cancer
September 15, 2015

BACKGROUND: Although enumeration of circulating tumor cells (CTCs) has shown some clinical value, the pool of CTCs contains a mixture of cells that contains additional information that can be extracted. The authors subclassified CTCs by shape features focusing on nuclear size and related this with clinical information. METHODS: A total of 148 blood samples were obtained from 57 patients with prostate cancer across the spectrum of metastatic states: no metastasis, nonvisceral metastasis, and visceral metastasis. CTCs captured and enumerated on NanoVelcro Chips (CytoLumina, Los Angeles, Calif) were subjected to pathologic review including nuclear size. The distribution of nuclear size was analyzed using a Gaussian mixture model. Correlations were made between CTC subpopulations and metastatic status. RESULTS: Statistical modeling of nuclear size distribution revealed 3 distinct subpopulations: large nuclear CTCs, small nuclear CTCs, and very small nuclear CTCs (vsnCTCs). Small nuclear CTCs and vsnCTC identified those patients with metastatic disease. However, vsnCTC counts alone were found to be elevated in patients with visceral metastases when compared with those without (0.36 ± 0.69 vs 1.95 ± 3.77 cells/mL blood; P<.001). Serial enumeration studies suggested the emergence of vsnCTCs occurred before the detection of visceral metastases. CONCLUSIONS: There are morphologic subsets of CTCs that can be identified by fundamental pathologic approaches, such as nuclear size measurement. The results of this observational study strongly suggest that CTCs contain relevant information regarding disease status. In particular, the detection of vsnCTCs was found to be correlated with the presence of visceral metastases and should be formally explored as a putative blood-borne biomarker to identify patients at risk of developing this clinical evolution of prostate cancer.

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Published In

Cancer

DOI

EISSN

1097-0142

Publication Date

September 15, 2015

Volume

121

Issue

18

Start / End Page

3240 / 3251

Location

United States

Related Subject Headings

  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • Neoplastic Cells, Circulating
  • Neoplasm Metastasis
  • Male
  • Humans
  • Cell Nucleus
  • 4206 Public health
  • 3211 Oncology and carcinogenesis
  • 1117 Public Health and Health Services
 

Citation

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ICMJE
MLA
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Chen, J.-F., Ho, H., Lichterman, J., Lu, Y.-T., Zhang, Y., Garcia, M. A., … Posadas, E. M. (2015). Subclassification of prostate cancer circulating tumor cells by nuclear size reveals very small nuclear circulating tumor cells in patients with visceral metastases. Cancer, 121(18), 3240–3251. https://doi.org/10.1002/cncr.29455
Chen, Jie-Fu, Hao Ho, Jake Lichterman, Yi-Tsung Lu, Yang Zhang, Mitch A. Garcia, Shang-Fu Chen, et al. “Subclassification of prostate cancer circulating tumor cells by nuclear size reveals very small nuclear circulating tumor cells in patients with visceral metastases.Cancer 121, no. 18 (September 15, 2015): 3240–51. https://doi.org/10.1002/cncr.29455.
Chen, Jie-Fu, et al. “Subclassification of prostate cancer circulating tumor cells by nuclear size reveals very small nuclear circulating tumor cells in patients with visceral metastases.Cancer, vol. 121, no. 18, Sept. 2015, pp. 3240–51. Pubmed, doi:10.1002/cncr.29455.
Chen J-F, Ho H, Lichterman J, Lu Y-T, Zhang Y, Garcia MA, Chen S-F, Liang A-J, Hodara E, Zhau HE, Hou S, Ahmed RS, Luthringer DJ, Huang J, Li K-C, Chung LWK, Ke Z, Tseng H-R, Posadas EM. Subclassification of prostate cancer circulating tumor cells by nuclear size reveals very small nuclear circulating tumor cells in patients with visceral metastases. Cancer. 2015 Sep 15;121(18):3240–3251.
Journal cover image

Published In

Cancer

DOI

EISSN

1097-0142

Publication Date

September 15, 2015

Volume

121

Issue

18

Start / End Page

3240 / 3251

Location

United States

Related Subject Headings

  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • Neoplastic Cells, Circulating
  • Neoplasm Metastasis
  • Male
  • Humans
  • Cell Nucleus
  • 4206 Public health
  • 3211 Oncology and carcinogenesis
  • 1117 Public Health and Health Services