Cytokeratin-19 and Mammaglobin gene expression in circulating tumor cells from metastatic breast cancer patients enrolled in North Central Cancer Treatment Group trials, N0234/336/436/437

Monica M. Reinholz, Kathleen A. Kitzmann, Kathleen Tenner, David Hillman, Amylou Dueck, Timothy James Hobday, Donald W Northfelt, Alvaro Moreno Aspitia, Vivek Roy, Betsy LaPlant, Jake B. Allred, Philip J. Stella, Wilma L. Lingle, Edith A. Perez

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Abstract

Purpose: To investigate the associations between baseline and posttreatment circulating tumor cell (CTC) gene expression and outcome of patients enrolled in four North Central Cancer Treatment Group metastatic breast cancer (MBC) trials in which specimens were shipped (at 4°C) from community-based sites to a reference laboratory (Mayo Clinic, Rochester, MN). Experimental Design: Blood was collected at treating sites from MBC patients before (baseline), during, and at the end of treatment with erlotinib + gemcitabine (N0234), sorafenib (N0336), irinotecan +cetuximab (N0436), or paclitaxel-poliglumex + capecitabine (N0437). CTCs from 10 mL of EDTA blood were enriched withCD45depletion, 24 to 30 hours postblood collection. Reverse transcription/quantitative PCR was used to determine cytokeratin-19 (CK19) and mammaglobin (MGB1) mRNA levels in CTCs from up to 13 (N0234), 16 (N0336), 18 (N0436), and 39 (N0437) patients. The gene expressions were normalized toβ 2-microglobulin and calibrated to healthy blood using the 2- ΔΔCq algorithm; positivity was defined as 2 or more. Results: CK19+mRNA cells were detected in 56% to 75% and MGB1+mRNA cells in 23% to 38% of 86 patients at baseline. CK19+mRNA cells were detected in 30% to 67% and MGB1+mRNA cells in 14% to 64% of 110 postbaseline serial samples. The presence of baseline CK19+mRNA cells (P = 0.01) but not MGB1+mRNA cells (P = 0.14) was significantly associated with shorter overall survival. A decrease in MGB1+mRNA levels (baseline-week 8) seemed to be associated with clinical response (P = 0.05). Conclusions: CTC gene expression analysis conducted by a reference laboratory is feasible when blood is collected from treating sites and processed 24 to 30 hours postcollection. The presence of baseline CK19+mRNA CTCs was associated with poor prognosis; a decrease in MGB1+mRNA CTCs may help predict response to therapy of MBC patients.

Original languageEnglish (US)
Pages (from-to)7183-7193
Number of pages11
JournalClinical Cancer Research
Volume17
Issue number22
DOIs
StatePublished - Nov 15 2011

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Keratin-19
Circulating Neoplastic Cells
Breast Neoplasms
Gene Expression
Messenger RNA
Neoplasms
Therapeutics
irinotecan
gemcitabine
Edetic Acid
Reverse Transcription
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Cytokeratin-19 and Mammaglobin gene expression in circulating tumor cells from metastatic breast cancer patients enrolled in North Central Cancer Treatment Group trials, N0234/336/436/437. / Reinholz, Monica M.; Kitzmann, Kathleen A.; Tenner, Kathleen; Hillman, David; Dueck, Amylou; Hobday, Timothy James; Northfelt, Donald W; Moreno Aspitia, Alvaro; Roy, Vivek; LaPlant, Betsy; Allred, Jake B.; Stella, Philip J.; Lingle, Wilma L.; Perez, Edith A.

In: Clinical Cancer Research, Vol. 17, No. 22, 15.11.2011, p. 7183-7193.

Research output: Contribution to journalArticle

Reinholz, Monica M. ; Kitzmann, Kathleen A. ; Tenner, Kathleen ; Hillman, David ; Dueck, Amylou ; Hobday, Timothy James ; Northfelt, Donald W ; Moreno Aspitia, Alvaro ; Roy, Vivek ; LaPlant, Betsy ; Allred, Jake B. ; Stella, Philip J. ; Lingle, Wilma L. ; Perez, Edith A. / Cytokeratin-19 and Mammaglobin gene expression in circulating tumor cells from metastatic breast cancer patients enrolled in North Central Cancer Treatment Group trials, N0234/336/436/437. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 22. pp. 7183-7193.
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title = "Cytokeratin-19 and Mammaglobin gene expression in circulating tumor cells from metastatic breast cancer patients enrolled in North Central Cancer Treatment Group trials, N0234/336/436/437",
abstract = "Purpose: To investigate the associations between baseline and posttreatment circulating tumor cell (CTC) gene expression and outcome of patients enrolled in four North Central Cancer Treatment Group metastatic breast cancer (MBC) trials in which specimens were shipped (at 4°C) from community-based sites to a reference laboratory (Mayo Clinic, Rochester, MN). Experimental Design: Blood was collected at treating sites from MBC patients before (baseline), during, and at the end of treatment with erlotinib + gemcitabine (N0234), sorafenib (N0336), irinotecan +cetuximab (N0436), or paclitaxel-poliglumex + capecitabine (N0437). CTCs from 10 mL of EDTA blood were enriched withCD45depletion, 24 to 30 hours postblood collection. Reverse transcription/quantitative PCR was used to determine cytokeratin-19 (CK19) and mammaglobin (MGB1) mRNA levels in CTCs from up to 13 (N0234), 16 (N0336), 18 (N0436), and 39 (N0437) patients. The gene expressions were normalized toβ 2-microglobulin and calibrated to healthy blood using the 2- ΔΔCq algorithm; positivity was defined as 2 or more. Results: CK19+mRNA cells were detected in 56{\%} to 75{\%} and MGB1+mRNA cells in 23{\%} to 38{\%} of 86 patients at baseline. CK19+mRNA cells were detected in 30{\%} to 67{\%} and MGB1+mRNA cells in 14{\%} to 64{\%} of 110 postbaseline serial samples. The presence of baseline CK19+mRNA cells (P = 0.01) but not MGB1+mRNA cells (P = 0.14) was significantly associated with shorter overall survival. A decrease in MGB1+mRNA levels (baseline-week 8) seemed to be associated with clinical response (P = 0.05). Conclusions: CTC gene expression analysis conducted by a reference laboratory is feasible when blood is collected from treating sites and processed 24 to 30 hours postcollection. The presence of baseline CK19+mRNA CTCs was associated with poor prognosis; a decrease in MGB1+mRNA CTCs may help predict response to therapy of MBC patients.",
author = "Reinholz, {Monica M.} and Kitzmann, {Kathleen A.} and Kathleen Tenner and David Hillman and Amylou Dueck and Hobday, {Timothy James} and Northfelt, {Donald W} and {Moreno Aspitia}, Alvaro and Vivek Roy and Betsy LaPlant and Allred, {Jake B.} and Stella, {Philip J.} and Lingle, {Wilma L.} and Perez, {Edith A.}",
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T1 - Cytokeratin-19 and Mammaglobin gene expression in circulating tumor cells from metastatic breast cancer patients enrolled in North Central Cancer Treatment Group trials, N0234/336/436/437

AU - Reinholz, Monica M.

AU - Kitzmann, Kathleen A.

AU - Tenner, Kathleen

AU - Hillman, David

AU - Dueck, Amylou

AU - Hobday, Timothy James

AU - Northfelt, Donald W

AU - Moreno Aspitia, Alvaro

AU - Roy, Vivek

AU - LaPlant, Betsy

AU - Allred, Jake B.

AU - Stella, Philip J.

AU - Lingle, Wilma L.

AU - Perez, Edith A.

PY - 2011/11/15

Y1 - 2011/11/15

N2 - Purpose: To investigate the associations between baseline and posttreatment circulating tumor cell (CTC) gene expression and outcome of patients enrolled in four North Central Cancer Treatment Group metastatic breast cancer (MBC) trials in which specimens were shipped (at 4°C) from community-based sites to a reference laboratory (Mayo Clinic, Rochester, MN). Experimental Design: Blood was collected at treating sites from MBC patients before (baseline), during, and at the end of treatment with erlotinib + gemcitabine (N0234), sorafenib (N0336), irinotecan +cetuximab (N0436), or paclitaxel-poliglumex + capecitabine (N0437). CTCs from 10 mL of EDTA blood were enriched withCD45depletion, 24 to 30 hours postblood collection. Reverse transcription/quantitative PCR was used to determine cytokeratin-19 (CK19) and mammaglobin (MGB1) mRNA levels in CTCs from up to 13 (N0234), 16 (N0336), 18 (N0436), and 39 (N0437) patients. The gene expressions were normalized toβ 2-microglobulin and calibrated to healthy blood using the 2- ΔΔCq algorithm; positivity was defined as 2 or more. Results: CK19+mRNA cells were detected in 56% to 75% and MGB1+mRNA cells in 23% to 38% of 86 patients at baseline. CK19+mRNA cells were detected in 30% to 67% and MGB1+mRNA cells in 14% to 64% of 110 postbaseline serial samples. The presence of baseline CK19+mRNA cells (P = 0.01) but not MGB1+mRNA cells (P = 0.14) was significantly associated with shorter overall survival. A decrease in MGB1+mRNA levels (baseline-week 8) seemed to be associated with clinical response (P = 0.05). Conclusions: CTC gene expression analysis conducted by a reference laboratory is feasible when blood is collected from treating sites and processed 24 to 30 hours postcollection. The presence of baseline CK19+mRNA CTCs was associated with poor prognosis; a decrease in MGB1+mRNA CTCs may help predict response to therapy of MBC patients.

AB - Purpose: To investigate the associations between baseline and posttreatment circulating tumor cell (CTC) gene expression and outcome of patients enrolled in four North Central Cancer Treatment Group metastatic breast cancer (MBC) trials in which specimens were shipped (at 4°C) from community-based sites to a reference laboratory (Mayo Clinic, Rochester, MN). Experimental Design: Blood was collected at treating sites from MBC patients before (baseline), during, and at the end of treatment with erlotinib + gemcitabine (N0234), sorafenib (N0336), irinotecan +cetuximab (N0436), or paclitaxel-poliglumex + capecitabine (N0437). CTCs from 10 mL of EDTA blood were enriched withCD45depletion, 24 to 30 hours postblood collection. Reverse transcription/quantitative PCR was used to determine cytokeratin-19 (CK19) and mammaglobin (MGB1) mRNA levels in CTCs from up to 13 (N0234), 16 (N0336), 18 (N0436), and 39 (N0437) patients. The gene expressions were normalized toβ 2-microglobulin and calibrated to healthy blood using the 2- ΔΔCq algorithm; positivity was defined as 2 or more. Results: CK19+mRNA cells were detected in 56% to 75% and MGB1+mRNA cells in 23% to 38% of 86 patients at baseline. CK19+mRNA cells were detected in 30% to 67% and MGB1+mRNA cells in 14% to 64% of 110 postbaseline serial samples. The presence of baseline CK19+mRNA cells (P = 0.01) but not MGB1+mRNA cells (P = 0.14) was significantly associated with shorter overall survival. A decrease in MGB1+mRNA levels (baseline-week 8) seemed to be associated with clinical response (P = 0.05). Conclusions: CTC gene expression analysis conducted by a reference laboratory is feasible when blood is collected from treating sites and processed 24 to 30 hours postcollection. The presence of baseline CK19+mRNA CTCs was associated with poor prognosis; a decrease in MGB1+mRNA CTCs may help predict response to therapy of MBC patients.

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