Circulating tumor cell isolation during resection of colorectal cancer lung and liver metastases: A prospective trial with different detection techniques

Jussuf T. Kaifi, Miriam Kunkel, Avisnata Das, Ramdane A. Harouaka, David T. Dicker, Guangfu Li, Junjia Zhu, Gary Clawson, Zhaohai Yang, Michael F. Reed, Niraj J. Gusani, Eric T. Kimchi, Kevin F. Staveley-O’Carroll, Siyang Zheng, Wafik S. El-Deiry

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: Colorectal cancer (CRC) metastasectomy improves survival, however most patient develop recurrences. Circulating tumor cells (CTCs) are an independent prognostic marker in stage IV CRC. We hypothesized that CTCs can be enriched during metastasectomy applying different isolation techniques. Methods: 25 CRC patients undergoing liver (16 (64%)) or lung (9 (36%)) metastasectomy were prospectively enrolled (clinicaltrial.gov identifier: NCT01722903). Central venous (liver) or radial artery (lung) tumor outflow blood (7.5 ml) was collected at incision, during resection, 30 min after resection, and on postoperative day (POD) 1. CTCs were quantified with 1. EpCAM-based CellSearch® system and 2. size-based isolation with a novel filter device (FMSA). CTCs were immunohistochemically identified using CellSearch®‘s criteria (cytokeratin 8/18/19+, CD45- cells containing a nucleus (DAPI+)). CTCs were also enriched with a centrifugation technique (OncoQuick®). Results: CTC numbers peaked during the resection with the FMSA in contrast to CellSearch® (mean CTC number during resection: FMSA: 22.56 (SEM 7.48) (p = 0.0281), CellSearch®: 0.87 (SEM ± 0.44) (p = 0.3018)). Comparing the 2 techniques, CTC quantity was significantly higher with the FMSA device (range 0–101) than CellSearch® (range 0–9) at each of the 4 time points examined (P < 0.05). Immunofluorescence staining of cultured CTCs revealed that CTCs have a combined epithelial (CK8/18/19) and macrophage (CD45/CD14) phenotype. Conclusions: Blood sampling during CRC metastasis resection is an opportunity to increase CTC capture efficiency. CTC isolation with the FMSA yields more CTCs than the CellSearch® system. Future studies should focus on characterization of single CTCs to identify targets for molecular therapy and immune escape mechanisms of cancer cells.

Original languageEnglish (US)
Pages (from-to)699-708
Number of pages10
JournalCancer Biology and Therapy
Volume16
Issue number5
DOIs
StatePublished - Jan 1 2015

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Circulating Neoplastic Cells
Cell Separation
Liver Neoplasms
Colorectal Neoplasms
Lung Neoplasms
Neoplasm Metastasis
Metastasectomy
Cell Count
Keratin-8
Cultured Tumor Cells
Keratin-18
Equipment and Supplies
Lung
Radial Artery
Liver
Centrifugation

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

Kaifi, Jussuf T. ; Kunkel, Miriam ; Das, Avisnata ; Harouaka, Ramdane A. ; Dicker, David T. ; Li, Guangfu ; Zhu, Junjia ; Clawson, Gary ; Yang, Zhaohai ; Reed, Michael F. ; Gusani, Niraj J. ; Kimchi, Eric T. ; Staveley-O’Carroll, Kevin F. ; Zheng, Siyang ; El-Deiry, Wafik S. / Circulating tumor cell isolation during resection of colorectal cancer lung and liver metastases : A prospective trial with different detection techniques. In: Cancer Biology and Therapy. 2015 ; Vol. 16, No. 5. pp. 699-708.
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title = "Circulating tumor cell isolation during resection of colorectal cancer lung and liver metastases: A prospective trial with different detection techniques",
abstract = "Background: Colorectal cancer (CRC) metastasectomy improves survival, however most patient develop recurrences. Circulating tumor cells (CTCs) are an independent prognostic marker in stage IV CRC. We hypothesized that CTCs can be enriched during metastasectomy applying different isolation techniques. Methods: 25 CRC patients undergoing liver (16 (64{\%})) or lung (9 (36{\%})) metastasectomy were prospectively enrolled (clinicaltrial.gov identifier: NCT01722903). Central venous (liver) or radial artery (lung) tumor outflow blood (7.5 ml) was collected at incision, during resection, 30 min after resection, and on postoperative day (POD) 1. CTCs were quantified with 1. EpCAM-based CellSearch{\circledR} system and 2. size-based isolation with a novel filter device (FMSA). CTCs were immunohistochemically identified using CellSearch{\circledR}‘s criteria (cytokeratin 8/18/19+, CD45- cells containing a nucleus (DAPI+)). CTCs were also enriched with a centrifugation technique (OncoQuick{\circledR}). Results: CTC numbers peaked during the resection with the FMSA in contrast to CellSearch{\circledR} (mean CTC number during resection: FMSA: 22.56 (SEM 7.48) (p = 0.0281), CellSearch{\circledR}: 0.87 (SEM ± 0.44) (p = 0.3018)). Comparing the 2 techniques, CTC quantity was significantly higher with the FMSA device (range 0–101) than CellSearch{\circledR} (range 0–9) at each of the 4 time points examined (P < 0.05). Immunofluorescence staining of cultured CTCs revealed that CTCs have a combined epithelial (CK8/18/19) and macrophage (CD45/CD14) phenotype. Conclusions: Blood sampling during CRC metastasis resection is an opportunity to increase CTC capture efficiency. CTC isolation with the FMSA yields more CTCs than the CellSearch{\circledR} system. Future studies should focus on characterization of single CTCs to identify targets for molecular therapy and immune escape mechanisms of cancer cells.",
author = "Kaifi, {Jussuf T.} and Miriam Kunkel and Avisnata Das and Harouaka, {Ramdane A.} and Dicker, {David T.} and Guangfu Li and Junjia Zhu and Gary Clawson and Zhaohai Yang and Reed, {Michael F.} and Gusani, {Niraj J.} and Kimchi, {Eric T.} and Staveley-O’Carroll, {Kevin F.} and Siyang Zheng and El-Deiry, {Wafik S.}",
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Circulating tumor cell isolation during resection of colorectal cancer lung and liver metastases : A prospective trial with different detection techniques. / Kaifi, Jussuf T.; Kunkel, Miriam; Das, Avisnata; Harouaka, Ramdane A.; Dicker, David T.; Li, Guangfu; Zhu, Junjia; Clawson, Gary; Yang, Zhaohai; Reed, Michael F.; Gusani, Niraj J.; Kimchi, Eric T.; Staveley-O’Carroll, Kevin F.; Zheng, Siyang; El-Deiry, Wafik S.

In: Cancer Biology and Therapy, Vol. 16, No. 5, 01.01.2015, p. 699-708.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Circulating tumor cell isolation during resection of colorectal cancer lung and liver metastases

T2 - A prospective trial with different detection techniques

AU - Kaifi, Jussuf T.

AU - Kunkel, Miriam

AU - Das, Avisnata

AU - Harouaka, Ramdane A.

AU - Dicker, David T.

AU - Li, Guangfu

AU - Zhu, Junjia

AU - Clawson, Gary

AU - Yang, Zhaohai

AU - Reed, Michael F.

AU - Gusani, Niraj J.

AU - Kimchi, Eric T.

AU - Staveley-O’Carroll, Kevin F.

AU - Zheng, Siyang

AU - El-Deiry, Wafik S.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background: Colorectal cancer (CRC) metastasectomy improves survival, however most patient develop recurrences. Circulating tumor cells (CTCs) are an independent prognostic marker in stage IV CRC. We hypothesized that CTCs can be enriched during metastasectomy applying different isolation techniques. Methods: 25 CRC patients undergoing liver (16 (64%)) or lung (9 (36%)) metastasectomy were prospectively enrolled (clinicaltrial.gov identifier: NCT01722903). Central venous (liver) or radial artery (lung) tumor outflow blood (7.5 ml) was collected at incision, during resection, 30 min after resection, and on postoperative day (POD) 1. CTCs were quantified with 1. EpCAM-based CellSearch® system and 2. size-based isolation with a novel filter device (FMSA). CTCs were immunohistochemically identified using CellSearch®‘s criteria (cytokeratin 8/18/19+, CD45- cells containing a nucleus (DAPI+)). CTCs were also enriched with a centrifugation technique (OncoQuick®). Results: CTC numbers peaked during the resection with the FMSA in contrast to CellSearch® (mean CTC number during resection: FMSA: 22.56 (SEM 7.48) (p = 0.0281), CellSearch®: 0.87 (SEM ± 0.44) (p = 0.3018)). Comparing the 2 techniques, CTC quantity was significantly higher with the FMSA device (range 0–101) than CellSearch® (range 0–9) at each of the 4 time points examined (P < 0.05). Immunofluorescence staining of cultured CTCs revealed that CTCs have a combined epithelial (CK8/18/19) and macrophage (CD45/CD14) phenotype. Conclusions: Blood sampling during CRC metastasis resection is an opportunity to increase CTC capture efficiency. CTC isolation with the FMSA yields more CTCs than the CellSearch® system. Future studies should focus on characterization of single CTCs to identify targets for molecular therapy and immune escape mechanisms of cancer cells.

AB - Background: Colorectal cancer (CRC) metastasectomy improves survival, however most patient develop recurrences. Circulating tumor cells (CTCs) are an independent prognostic marker in stage IV CRC. We hypothesized that CTCs can be enriched during metastasectomy applying different isolation techniques. Methods: 25 CRC patients undergoing liver (16 (64%)) or lung (9 (36%)) metastasectomy were prospectively enrolled (clinicaltrial.gov identifier: NCT01722903). Central venous (liver) or radial artery (lung) tumor outflow blood (7.5 ml) was collected at incision, during resection, 30 min after resection, and on postoperative day (POD) 1. CTCs were quantified with 1. EpCAM-based CellSearch® system and 2. size-based isolation with a novel filter device (FMSA). CTCs were immunohistochemically identified using CellSearch®‘s criteria (cytokeratin 8/18/19+, CD45- cells containing a nucleus (DAPI+)). CTCs were also enriched with a centrifugation technique (OncoQuick®). Results: CTC numbers peaked during the resection with the FMSA in contrast to CellSearch® (mean CTC number during resection: FMSA: 22.56 (SEM 7.48) (p = 0.0281), CellSearch®: 0.87 (SEM ± 0.44) (p = 0.3018)). Comparing the 2 techniques, CTC quantity was significantly higher with the FMSA device (range 0–101) than CellSearch® (range 0–9) at each of the 4 time points examined (P < 0.05). Immunofluorescence staining of cultured CTCs revealed that CTCs have a combined epithelial (CK8/18/19) and macrophage (CD45/CD14) phenotype. Conclusions: Blood sampling during CRC metastasis resection is an opportunity to increase CTC capture efficiency. CTC isolation with the FMSA yields more CTCs than the CellSearch® system. Future studies should focus on characterization of single CTCs to identify targets for molecular therapy and immune escape mechanisms of cancer cells.

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