Circulating free DNA in a screening program for early colorectal cancer detection

Federica Perrone, Andrea Lampis, Claudia Bertan, Paolo Verderio, Chiara M. Ciniselli, Sara Pizzamiglio, Milo Frattini, Martina Nucifora, Francesca Molinari, Gianfranco Gallino, Manuela Gariboldi, Emanuele Meroni, Ermanno Leo, Marco A. Pierotti, Silvana Pilotti

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Aims and background. The quantification and molecular characterization of circulating free DNA (cfDNA) have attracted much interest as new and promising, noninvasive means of detecting and monitoring the presence of surgical resectable colorectal cancer (CRC). Instead, the role of cfDNA in the early detection of malignant and premalignant colorectal lesions is still unclear. The aim of this study was to evaluate the predictive power of the quantification and KRAS status of cfDNA in detecting early colorectal lesions in plasma from healthy high-risk subjects. Methods. The study population consisted of 170 consecutive healthy high-risk subjects aged >50 years who participated in the screening program promoted by the Local Health Service (ASL-Milano) for early CRC detection and who underwent endoscopic examination after being found positive at fecal occult blood test (FOBT). Thirty-four participants had malignant lesions consisting of 12 adenocarcinomas (at an early stage in half of the cases) and 22 instances of high-grade intraepithelial neoplasia (HGIN) in adenomas; 73 participants had premalignant lesions (adenomas and hyperplasia), and 63 participants had no lesions. Plasma cfDNA was quantified by quantitative real-time PCR and analyzed for KRAS mutations by a mutant-enriched PCR. KRAS status was assessed also in matched adenocarcinoma and HGIN tissues. The distribution of cfDNA concentrations among FOBT-positive subjects with diagnosed lesion (cases) was compared with that of FOBT-positive subjects without lesions (controls) and its predictive capability (AUC) was assessed. Results. The predictive capability of cfDNA levels was satisfactory in predicting adenocarcinomas (AUC 0.709; 95% CI, 0.508-0.909) but not HGIN and premalignant lesions. The rate of KRAS mutations in plasma was low (5/170 = 3%) compared with the rate observed in the matched adenocarcinoma and HGIN tissues (45%). Conclusions. The use of cfDNA quantification to predict adenocarcinoma at an early stage in high-risk (aged >50 years and FOBT positive) subjects seems to be promising but needs more sensitive methods to improve cfDNA detection. Copyright - Il Pensiero Scientifico Editore.

Original languageEnglish
Pages (from-to)115-121
Number of pages7
JournalTumori
Volume100
Issue number2
DOIs
Publication statusPublished - 2014

Fingerprint

Early Detection of Cancer
Colorectal Neoplasms
Occult Blood
DNA
Hematologic Tests
Adenocarcinoma
Adenoma
Area Under Curve
Neoplasms
Mutation Rate
Health Services
Hyperplasia
Real-Time Polymerase Chain Reaction
Polymerase Chain Reaction
Mutation
Population

Keywords

  • Circulating free DNA
  • Colorectal cancer
  • Early diagnosis
  • Plasma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Perrone, F., Lampis, A., Bertan, C., Verderio, P., Ciniselli, C. M., Pizzamiglio, S., ... Pilotti, S. (2014). Circulating free DNA in a screening program for early colorectal cancer detection. Tumori, 100(2), 115-121. https://doi.org/10.1700/1491.16389

Circulating free DNA in a screening program for early colorectal cancer detection. / Perrone, Federica; Lampis, Andrea; Bertan, Claudia; Verderio, Paolo; Ciniselli, Chiara M.; Pizzamiglio, Sara; Frattini, Milo; Nucifora, Martina; Molinari, Francesca; Gallino, Gianfranco; Gariboldi, Manuela; Meroni, Emanuele; Leo, Ermanno; Pierotti, Marco A.; Pilotti, Silvana.

In: Tumori, Vol. 100, No. 2, 2014, p. 115-121.

Research output: Contribution to journalArticle

Perrone, F, Lampis, A, Bertan, C, Verderio, P, Ciniselli, CM, Pizzamiglio, S, Frattini, M, Nucifora, M, Molinari, F, Gallino, G, Gariboldi, M, Meroni, E, Leo, E, Pierotti, MA & Pilotti, S 2014, 'Circulating free DNA in a screening program for early colorectal cancer detection', Tumori, vol. 100, no. 2, pp. 115-121. https://doi.org/10.1700/1491.16389
Perrone, Federica ; Lampis, Andrea ; Bertan, Claudia ; Verderio, Paolo ; Ciniselli, Chiara M. ; Pizzamiglio, Sara ; Frattini, Milo ; Nucifora, Martina ; Molinari, Francesca ; Gallino, Gianfranco ; Gariboldi, Manuela ; Meroni, Emanuele ; Leo, Ermanno ; Pierotti, Marco A. ; Pilotti, Silvana. / Circulating free DNA in a screening program for early colorectal cancer detection. In: Tumori. 2014 ; Vol. 100, No. 2. pp. 115-121.
@article{ebe3c84c4a9b4a81b085f1f979df96b2,
title = "Circulating free DNA in a screening program for early colorectal cancer detection",
abstract = "Aims and background. The quantification and molecular characterization of circulating free DNA (cfDNA) have attracted much interest as new and promising, noninvasive means of detecting and monitoring the presence of surgical resectable colorectal cancer (CRC). Instead, the role of cfDNA in the early detection of malignant and premalignant colorectal lesions is still unclear. The aim of this study was to evaluate the predictive power of the quantification and KRAS status of cfDNA in detecting early colorectal lesions in plasma from healthy high-risk subjects. Methods. The study population consisted of 170 consecutive healthy high-risk subjects aged >50 years who participated in the screening program promoted by the Local Health Service (ASL-Milano) for early CRC detection and who underwent endoscopic examination after being found positive at fecal occult blood test (FOBT). Thirty-four participants had malignant lesions consisting of 12 adenocarcinomas (at an early stage in half of the cases) and 22 instances of high-grade intraepithelial neoplasia (HGIN) in adenomas; 73 participants had premalignant lesions (adenomas and hyperplasia), and 63 participants had no lesions. Plasma cfDNA was quantified by quantitative real-time PCR and analyzed for KRAS mutations by a mutant-enriched PCR. KRAS status was assessed also in matched adenocarcinoma and HGIN tissues. The distribution of cfDNA concentrations among FOBT-positive subjects with diagnosed lesion (cases) was compared with that of FOBT-positive subjects without lesions (controls) and its predictive capability (AUC) was assessed. Results. The predictive capability of cfDNA levels was satisfactory in predicting adenocarcinomas (AUC 0.709; 95{\%} CI, 0.508-0.909) but not HGIN and premalignant lesions. The rate of KRAS mutations in plasma was low (5/170 = 3{\%}) compared with the rate observed in the matched adenocarcinoma and HGIN tissues (45{\%}). Conclusions. The use of cfDNA quantification to predict adenocarcinoma at an early stage in high-risk (aged >50 years and FOBT positive) subjects seems to be promising but needs more sensitive methods to improve cfDNA detection. Copyright - Il Pensiero Scientifico Editore.",
keywords = "Circulating free DNA, Colorectal cancer, Early diagnosis, Plasma",
author = "Federica Perrone and Andrea Lampis and Claudia Bertan and Paolo Verderio and Ciniselli, {Chiara M.} and Sara Pizzamiglio and Milo Frattini and Martina Nucifora and Francesca Molinari and Gianfranco Gallino and Manuela Gariboldi and Emanuele Meroni and Ermanno Leo and Pierotti, {Marco A.} and Silvana Pilotti",
year = "2014",
doi = "10.1700/1491.16389",
language = "English",
volume = "100",
pages = "115--121",
journal = "Tumori",
issn = "0300-8916",
publisher = "SAGE Publications Ltd",
number = "2",

}

TY - JOUR

T1 - Circulating free DNA in a screening program for early colorectal cancer detection

AU - Perrone, Federica

AU - Lampis, Andrea

AU - Bertan, Claudia

AU - Verderio, Paolo

AU - Ciniselli, Chiara M.

AU - Pizzamiglio, Sara

AU - Frattini, Milo

AU - Nucifora, Martina

AU - Molinari, Francesca

AU - Gallino, Gianfranco

AU - Gariboldi, Manuela

AU - Meroni, Emanuele

AU - Leo, Ermanno

AU - Pierotti, Marco A.

AU - Pilotti, Silvana

PY - 2014

Y1 - 2014

N2 - Aims and background. The quantification and molecular characterization of circulating free DNA (cfDNA) have attracted much interest as new and promising, noninvasive means of detecting and monitoring the presence of surgical resectable colorectal cancer (CRC). Instead, the role of cfDNA in the early detection of malignant and premalignant colorectal lesions is still unclear. The aim of this study was to evaluate the predictive power of the quantification and KRAS status of cfDNA in detecting early colorectal lesions in plasma from healthy high-risk subjects. Methods. The study population consisted of 170 consecutive healthy high-risk subjects aged >50 years who participated in the screening program promoted by the Local Health Service (ASL-Milano) for early CRC detection and who underwent endoscopic examination after being found positive at fecal occult blood test (FOBT). Thirty-four participants had malignant lesions consisting of 12 adenocarcinomas (at an early stage in half of the cases) and 22 instances of high-grade intraepithelial neoplasia (HGIN) in adenomas; 73 participants had premalignant lesions (adenomas and hyperplasia), and 63 participants had no lesions. Plasma cfDNA was quantified by quantitative real-time PCR and analyzed for KRAS mutations by a mutant-enriched PCR. KRAS status was assessed also in matched adenocarcinoma and HGIN tissues. The distribution of cfDNA concentrations among FOBT-positive subjects with diagnosed lesion (cases) was compared with that of FOBT-positive subjects without lesions (controls) and its predictive capability (AUC) was assessed. Results. The predictive capability of cfDNA levels was satisfactory in predicting adenocarcinomas (AUC 0.709; 95% CI, 0.508-0.909) but not HGIN and premalignant lesions. The rate of KRAS mutations in plasma was low (5/170 = 3%) compared with the rate observed in the matched adenocarcinoma and HGIN tissues (45%). Conclusions. The use of cfDNA quantification to predict adenocarcinoma at an early stage in high-risk (aged >50 years and FOBT positive) subjects seems to be promising but needs more sensitive methods to improve cfDNA detection. Copyright - Il Pensiero Scientifico Editore.

AB - Aims and background. The quantification and molecular characterization of circulating free DNA (cfDNA) have attracted much interest as new and promising, noninvasive means of detecting and monitoring the presence of surgical resectable colorectal cancer (CRC). Instead, the role of cfDNA in the early detection of malignant and premalignant colorectal lesions is still unclear. The aim of this study was to evaluate the predictive power of the quantification and KRAS status of cfDNA in detecting early colorectal lesions in plasma from healthy high-risk subjects. Methods. The study population consisted of 170 consecutive healthy high-risk subjects aged >50 years who participated in the screening program promoted by the Local Health Service (ASL-Milano) for early CRC detection and who underwent endoscopic examination after being found positive at fecal occult blood test (FOBT). Thirty-four participants had malignant lesions consisting of 12 adenocarcinomas (at an early stage in half of the cases) and 22 instances of high-grade intraepithelial neoplasia (HGIN) in adenomas; 73 participants had premalignant lesions (adenomas and hyperplasia), and 63 participants had no lesions. Plasma cfDNA was quantified by quantitative real-time PCR and analyzed for KRAS mutations by a mutant-enriched PCR. KRAS status was assessed also in matched adenocarcinoma and HGIN tissues. The distribution of cfDNA concentrations among FOBT-positive subjects with diagnosed lesion (cases) was compared with that of FOBT-positive subjects without lesions (controls) and its predictive capability (AUC) was assessed. Results. The predictive capability of cfDNA levels was satisfactory in predicting adenocarcinomas (AUC 0.709; 95% CI, 0.508-0.909) but not HGIN and premalignant lesions. The rate of KRAS mutations in plasma was low (5/170 = 3%) compared with the rate observed in the matched adenocarcinoma and HGIN tissues (45%). Conclusions. The use of cfDNA quantification to predict adenocarcinoma at an early stage in high-risk (aged >50 years and FOBT positive) subjects seems to be promising but needs more sensitive methods to improve cfDNA detection. Copyright - Il Pensiero Scientifico Editore.

KW - Circulating free DNA

KW - Colorectal cancer

KW - Early diagnosis

KW - Plasma

UR - http://www.scopus.com/inward/record.url?scp=84901468108&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901468108&partnerID=8YFLogxK

U2 - 10.1700/1491.16389

DO - 10.1700/1491.16389

M3 - Article

VL - 100

SP - 115

EP - 121

JO - Tumori

JF - Tumori

SN - 0300-8916

IS - 2

ER -