Detection of blood-borne cells in colorectal cancer patients by nested reverse transcription-polymerase chain reaction for carcinoembryonic antigen messenger RNA

Longitudinal analyses and demonstration of its potential importance as an adjunct to multiple serum markers

F. Guadagni, J. Kantor, S. Aloe, M. D. Carone, A. Spila, R. D'Alessandro, M. R. Abbolito, M. Cosimelli, F. Graziano, F. Carboni, S. Carlini, P. Perri, F. Sciarretta, J. W. Greiner, S. V S Kashmiri, S. M. Steinberg, M. Roselli, J. Schlom

Research output: Contribution to journalArticle

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Abstract

The use of reverse transeription-PCR (RT-PCR) to analyze cells in the blood of cancer patients for the detection of mRNA expressed in tumor cells has implications for both the prognosis and the monitoring of cancer patients for the efficacy of established or experimental therapies. Carcinoembryonic antigen (CEA) is expressed on ∼95% of colorectal, gastric, and pancreatic tumors, and on the majority of breast, non-small cell lung, and head and neck carcinomas. CEA shed in serum is useful as a marker in only ∼50% of colorectal cancer patients and rarely is shed by some other carcinoma types. RT-PCR has been used previously to detect CEA mRNA in cells in the blood and lymph nodes of cancer patients. Under the assay conditions validated in the studies reported here, 34 of 51 (67%) patients with different stages of colorectal cancer had blood cells that were positive by RT-PCR forCEA mRNA, whereas none of 18 patients with colonic polyps were positive; 2 of 60 apparently healthy individuals (who were age and sex matched with the carcinoma patients and were part of a colon cancer screening program as controls) were marginally positive. The results of CEA PCR in the blood of the carcinoma patients and the other groups showed strong statistical correlation with the disease (P2 <0.0001). Analyses were carried out to detect both serum CEA protein levels and CEA mRNA in blood cells of colorectal carcinoma patients by RT-PCR. For all stages of disease, 18 of 51 patients (35%) were positive for serum CEA, whereas 35 of 51 (69%) were positive by RT-PCR. More importantly, only 5 of 23 (20%) of stage B and C colorectal cancer patients were positive for serum CEA, whereas 16 of 23 (70%) were positive by RT-PCR. The use of two other serum markers (CA19.9 and CA72-4) for colorectal cancer in combination with serum CEA scored two additional patients as positive; both were positive by RT-PCR for CEA mRNA. Pilot long-term longitudinal studies conducted before and after surgery identified some patients with CEA mRNA in blood cells that were negative for all serum markers, who eventually developed clinical metastatic disease. The studies reported here are the first to correlate RT-PCR results for CEA mRNA in blood cells with one or more serum markers for patients with different stages of colorectal cancer, and are the first long-term longitudinal studies to use RT-PCR to detect CEA mRNA in blood cells of cancer patients. Larger cohorts will be required in future studies to define the impact, if any, of this technology on prognosis and-or disease monitoring.

Original languageEnglish
Pages (from-to)2523-2532
Number of pages10
JournalCancer Research
Volume61
Issue number6
Publication statusPublished - Mar 15 2001

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Carcinoembryonic Antigen
Reverse Transcription
Colorectal Neoplasms
Blood Cells
Biomarkers
Polymerase Chain Reaction
Messenger RNA
Carcinoma
Neoplasms
Serum
Longitudinal Studies
Colonic Polyps
Investigational Therapies
Physiologic Monitoring
Early Detection of Cancer
Colonic Neoplasms
Stomach
Breast
Neck

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Detection of blood-borne cells in colorectal cancer patients by nested reverse transcription-polymerase chain reaction for carcinoembryonic antigen messenger RNA : Longitudinal analyses and demonstration of its potential importance as an adjunct to multiple serum markers. / Guadagni, F.; Kantor, J.; Aloe, S.; Carone, M. D.; Spila, A.; D'Alessandro, R.; Abbolito, M. R.; Cosimelli, M.; Graziano, F.; Carboni, F.; Carlini, S.; Perri, P.; Sciarretta, F.; Greiner, J. W.; Kashmiri, S. V S; Steinberg, S. M.; Roselli, M.; Schlom, J.

In: Cancer Research, Vol. 61, No. 6, 15.03.2001, p. 2523-2532.

Research output: Contribution to journalArticle

Guadagni, F, Kantor, J, Aloe, S, Carone, MD, Spila, A, D'Alessandro, R, Abbolito, MR, Cosimelli, M, Graziano, F, Carboni, F, Carlini, S, Perri, P, Sciarretta, F, Greiner, JW, Kashmiri, SVS, Steinberg, SM, Roselli, M & Schlom, J 2001, 'Detection of blood-borne cells in colorectal cancer patients by nested reverse transcription-polymerase chain reaction for carcinoembryonic antigen messenger RNA: Longitudinal analyses and demonstration of its potential importance as an adjunct to multiple serum markers', Cancer Research, vol. 61, no. 6, pp. 2523-2532.
Guadagni, F. ; Kantor, J. ; Aloe, S. ; Carone, M. D. ; Spila, A. ; D'Alessandro, R. ; Abbolito, M. R. ; Cosimelli, M. ; Graziano, F. ; Carboni, F. ; Carlini, S. ; Perri, P. ; Sciarretta, F. ; Greiner, J. W. ; Kashmiri, S. V S ; Steinberg, S. M. ; Roselli, M. ; Schlom, J. / Detection of blood-borne cells in colorectal cancer patients by nested reverse transcription-polymerase chain reaction for carcinoembryonic antigen messenger RNA : Longitudinal analyses and demonstration of its potential importance as an adjunct to multiple serum markers. In: Cancer Research. 2001 ; Vol. 61, No. 6. pp. 2523-2532.
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abstract = "The use of reverse transeription-PCR (RT-PCR) to analyze cells in the blood of cancer patients for the detection of mRNA expressed in tumor cells has implications for both the prognosis and the monitoring of cancer patients for the efficacy of established or experimental therapies. Carcinoembryonic antigen (CEA) is expressed on ∼95{\%} of colorectal, gastric, and pancreatic tumors, and on the majority of breast, non-small cell lung, and head and neck carcinomas. CEA shed in serum is useful as a marker in only ∼50{\%} of colorectal cancer patients and rarely is shed by some other carcinoma types. RT-PCR has been used previously to detect CEA mRNA in cells in the blood and lymph nodes of cancer patients. Under the assay conditions validated in the studies reported here, 34 of 51 (67{\%}) patients with different stages of colorectal cancer had blood cells that were positive by RT-PCR forCEA mRNA, whereas none of 18 patients with colonic polyps were positive; 2 of 60 apparently healthy individuals (who were age and sex matched with the carcinoma patients and were part of a colon cancer screening program as controls) were marginally positive. The results of CEA PCR in the blood of the carcinoma patients and the other groups showed strong statistical correlation with the disease (P2 <0.0001). Analyses were carried out to detect both serum CEA protein levels and CEA mRNA in blood cells of colorectal carcinoma patients by RT-PCR. For all stages of disease, 18 of 51 patients (35{\%}) were positive for serum CEA, whereas 35 of 51 (69{\%}) were positive by RT-PCR. More importantly, only 5 of 23 (20{\%}) of stage B and C colorectal cancer patients were positive for serum CEA, whereas 16 of 23 (70{\%}) were positive by RT-PCR. The use of two other serum markers (CA19.9 and CA72-4) for colorectal cancer in combination with serum CEA scored two additional patients as positive; both were positive by RT-PCR for CEA mRNA. Pilot long-term longitudinal studies conducted before and after surgery identified some patients with CEA mRNA in blood cells that were negative for all serum markers, who eventually developed clinical metastatic disease. The studies reported here are the first to correlate RT-PCR results for CEA mRNA in blood cells with one or more serum markers for patients with different stages of colorectal cancer, and are the first long-term longitudinal studies to use RT-PCR to detect CEA mRNA in blood cells of cancer patients. Larger cohorts will be required in future studies to define the impact, if any, of this technology on prognosis and-or disease monitoring.",
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T2 - Longitudinal analyses and demonstration of its potential importance as an adjunct to multiple serum markers

AU - Guadagni, F.

AU - Kantor, J.

AU - Aloe, S.

AU - Carone, M. D.

AU - Spila, A.

AU - D'Alessandro, R.

AU - Abbolito, M. R.

AU - Cosimelli, M.

AU - Graziano, F.

AU - Carboni, F.

AU - Carlini, S.

AU - Perri, P.

AU - Sciarretta, F.

AU - Greiner, J. W.

AU - Kashmiri, S. V S

AU - Steinberg, S. M.

AU - Roselli, M.

AU - Schlom, J.

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N2 - The use of reverse transeription-PCR (RT-PCR) to analyze cells in the blood of cancer patients for the detection of mRNA expressed in tumor cells has implications for both the prognosis and the monitoring of cancer patients for the efficacy of established or experimental therapies. Carcinoembryonic antigen (CEA) is expressed on ∼95% of colorectal, gastric, and pancreatic tumors, and on the majority of breast, non-small cell lung, and head and neck carcinomas. CEA shed in serum is useful as a marker in only ∼50% of colorectal cancer patients and rarely is shed by some other carcinoma types. RT-PCR has been used previously to detect CEA mRNA in cells in the blood and lymph nodes of cancer patients. Under the assay conditions validated in the studies reported here, 34 of 51 (67%) patients with different stages of colorectal cancer had blood cells that were positive by RT-PCR forCEA mRNA, whereas none of 18 patients with colonic polyps were positive; 2 of 60 apparently healthy individuals (who were age and sex matched with the carcinoma patients and were part of a colon cancer screening program as controls) were marginally positive. The results of CEA PCR in the blood of the carcinoma patients and the other groups showed strong statistical correlation with the disease (P2 <0.0001). Analyses were carried out to detect both serum CEA protein levels and CEA mRNA in blood cells of colorectal carcinoma patients by RT-PCR. For all stages of disease, 18 of 51 patients (35%) were positive for serum CEA, whereas 35 of 51 (69%) were positive by RT-PCR. More importantly, only 5 of 23 (20%) of stage B and C colorectal cancer patients were positive for serum CEA, whereas 16 of 23 (70%) were positive by RT-PCR. The use of two other serum markers (CA19.9 and CA72-4) for colorectal cancer in combination with serum CEA scored two additional patients as positive; both were positive by RT-PCR for CEA mRNA. Pilot long-term longitudinal studies conducted before and after surgery identified some patients with CEA mRNA in blood cells that were negative for all serum markers, who eventually developed clinical metastatic disease. The studies reported here are the first to correlate RT-PCR results for CEA mRNA in blood cells with one or more serum markers for patients with different stages of colorectal cancer, and are the first long-term longitudinal studies to use RT-PCR to detect CEA mRNA in blood cells of cancer patients. Larger cohorts will be required in future studies to define the impact, if any, of this technology on prognosis and-or disease monitoring.

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