Automated sputum cytometry for detection of intraepithelial neoplasias in the lung

Gerald Li, Martial Guillaud, Jean Leriche, Annette McWilliams, Adi Gazdar, Stephen Lam, Calum MacAulay

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Despite the benefits of early lung cancer detection, no effective strategy for early screening and treatment exists, partly due to a lack of effective surrogate biomarkers. Our novel sputum biomarker, the Combined Score (CS), uses automated image cytometric analysis of ploidy and nuclear morphology to detect subtle intraepithelial changes that often precede lung tumours. Methods: 2249 sputum samples from 1795 high-risk patients enrolled in ongoing chemoprevention trials were subjected to automated quantitative image cytometry after Feulgen-thionin staining. Samples from normal histopathology patients were compared against samples from carcinoma in situ (CIS) and cancer patients to train the CS. Results: CS correlates with several lung cancer risk factors, including histopathological grade, age, smoking status, and p53 and Ki67 immunostaining. At 50% specificity, CS detected 78% of all highest-risk subjects-those with CIS or worse plus those with moderate or severe dysplasia and abnormal nuclear morphology. Conclusion: CS is a powerful yet minimally invasive tool for rapid and inexpensive risk assessment for the presence of precancerous lung lesions, enabling enrichment of chemoprevention trials with highest-risk dysplasias. CS correlates with other biomarkers, so CS may find use as a surrogate biomarker for patient assessment and as an endpoint in chemoprevention clinical trials.

Original languageEnglish (US)
Pages (from-to)187-201
Number of pages15
JournalAnalytical Cellular Pathology
Volume35
Issue number3
DOIs
StatePublished - 2012

Fingerprint

Sputum
Chemoprevention
Biomarkers
Lung
Carcinoma in Situ
Lung Neoplasms
Neoplasms
Thionins
Image Cytometry
Ploidies
Early Detection of Cancer
Smoking
Clinical Trials
Staining and Labeling
Therapeutics

Keywords

  • Biomarkers and intervention
  • Biomarkers and intervention studies
  • Cancer surveillance and screening
  • Chemoprevention
  • Intermediate or pre-neoplastic markers and risk factors
  • Intraepithelial neoplasia (IEN)
  • Lung cancer
  • Risk assessment

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Pathology and Forensic Medicine
  • Cell Biology

Cite this

Li, G., Guillaud, M., Leriche, J., McWilliams, A., Gazdar, A., Lam, S., & MacAulay, C. (2012). Automated sputum cytometry for detection of intraepithelial neoplasias in the lung. Analytical Cellular Pathology, 35(3), 187-201. https://doi.org/10.3233/ACP-2012-0053

Automated sputum cytometry for detection of intraepithelial neoplasias in the lung. / Li, Gerald; Guillaud, Martial; Leriche, Jean; McWilliams, Annette; Gazdar, Adi; Lam, Stephen; MacAulay, Calum.

In: Analytical Cellular Pathology, Vol. 35, No. 3, 2012, p. 187-201.

Research output: Contribution to journalArticle

Li, G, Guillaud, M, Leriche, J, McWilliams, A, Gazdar, A, Lam, S & MacAulay, C 2012, 'Automated sputum cytometry for detection of intraepithelial neoplasias in the lung', Analytical Cellular Pathology, vol. 35, no. 3, pp. 187-201. https://doi.org/10.3233/ACP-2012-0053
Li, Gerald ; Guillaud, Martial ; Leriche, Jean ; McWilliams, Annette ; Gazdar, Adi ; Lam, Stephen ; MacAulay, Calum. / Automated sputum cytometry for detection of intraepithelial neoplasias in the lung. In: Analytical Cellular Pathology. 2012 ; Vol. 35, No. 3. pp. 187-201.
@article{df1a61da1b594dc78e2f114076ddada7,
title = "Automated sputum cytometry for detection of intraepithelial neoplasias in the lung",
abstract = "Background: Despite the benefits of early lung cancer detection, no effective strategy for early screening and treatment exists, partly due to a lack of effective surrogate biomarkers. Our novel sputum biomarker, the Combined Score (CS), uses automated image cytometric analysis of ploidy and nuclear morphology to detect subtle intraepithelial changes that often precede lung tumours. Methods: 2249 sputum samples from 1795 high-risk patients enrolled in ongoing chemoprevention trials were subjected to automated quantitative image cytometry after Feulgen-thionin staining. Samples from normal histopathology patients were compared against samples from carcinoma in situ (CIS) and cancer patients to train the CS. Results: CS correlates with several lung cancer risk factors, including histopathological grade, age, smoking status, and p53 and Ki67 immunostaining. At 50{\%} specificity, CS detected 78{\%} of all highest-risk subjects-those with CIS or worse plus those with moderate or severe dysplasia and abnormal nuclear morphology. Conclusion: CS is a powerful yet minimally invasive tool for rapid and inexpensive risk assessment for the presence of precancerous lung lesions, enabling enrichment of chemoprevention trials with highest-risk dysplasias. CS correlates with other biomarkers, so CS may find use as a surrogate biomarker for patient assessment and as an endpoint in chemoprevention clinical trials.",
keywords = "Biomarkers and intervention, Biomarkers and intervention studies, Cancer surveillance and screening, Chemoprevention, Intermediate or pre-neoplastic markers and risk factors, Intraepithelial neoplasia (IEN), Lung cancer, Risk assessment",
author = "Gerald Li and Martial Guillaud and Jean Leriche and Annette McWilliams and Adi Gazdar and Stephen Lam and Calum MacAulay",
year = "2012",
doi = "10.3233/ACP-2012-0053",
language = "English (US)",
volume = "35",
pages = "187--201",
journal = "Analytical Cellular Pathology",
issn = "2210-7177",
publisher = "IOS Press",
number = "3",

}

TY - JOUR

T1 - Automated sputum cytometry for detection of intraepithelial neoplasias in the lung

AU - Li, Gerald

AU - Guillaud, Martial

AU - Leriche, Jean

AU - McWilliams, Annette

AU - Gazdar, Adi

AU - Lam, Stephen

AU - MacAulay, Calum

PY - 2012

Y1 - 2012

N2 - Background: Despite the benefits of early lung cancer detection, no effective strategy for early screening and treatment exists, partly due to a lack of effective surrogate biomarkers. Our novel sputum biomarker, the Combined Score (CS), uses automated image cytometric analysis of ploidy and nuclear morphology to detect subtle intraepithelial changes that often precede lung tumours. Methods: 2249 sputum samples from 1795 high-risk patients enrolled in ongoing chemoprevention trials were subjected to automated quantitative image cytometry after Feulgen-thionin staining. Samples from normal histopathology patients were compared against samples from carcinoma in situ (CIS) and cancer patients to train the CS. Results: CS correlates with several lung cancer risk factors, including histopathological grade, age, smoking status, and p53 and Ki67 immunostaining. At 50% specificity, CS detected 78% of all highest-risk subjects-those with CIS or worse plus those with moderate or severe dysplasia and abnormal nuclear morphology. Conclusion: CS is a powerful yet minimally invasive tool for rapid and inexpensive risk assessment for the presence of precancerous lung lesions, enabling enrichment of chemoprevention trials with highest-risk dysplasias. CS correlates with other biomarkers, so CS may find use as a surrogate biomarker for patient assessment and as an endpoint in chemoprevention clinical trials.

AB - Background: Despite the benefits of early lung cancer detection, no effective strategy for early screening and treatment exists, partly due to a lack of effective surrogate biomarkers. Our novel sputum biomarker, the Combined Score (CS), uses automated image cytometric analysis of ploidy and nuclear morphology to detect subtle intraepithelial changes that often precede lung tumours. Methods: 2249 sputum samples from 1795 high-risk patients enrolled in ongoing chemoprevention trials were subjected to automated quantitative image cytometry after Feulgen-thionin staining. Samples from normal histopathology patients were compared against samples from carcinoma in situ (CIS) and cancer patients to train the CS. Results: CS correlates with several lung cancer risk factors, including histopathological grade, age, smoking status, and p53 and Ki67 immunostaining. At 50% specificity, CS detected 78% of all highest-risk subjects-those with CIS or worse plus those with moderate or severe dysplasia and abnormal nuclear morphology. Conclusion: CS is a powerful yet minimally invasive tool for rapid and inexpensive risk assessment for the presence of precancerous lung lesions, enabling enrichment of chemoprevention trials with highest-risk dysplasias. CS correlates with other biomarkers, so CS may find use as a surrogate biomarker for patient assessment and as an endpoint in chemoprevention clinical trials.

KW - Biomarkers and intervention

KW - Biomarkers and intervention studies

KW - Cancer surveillance and screening

KW - Chemoprevention

KW - Intermediate or pre-neoplastic markers and risk factors

KW - Intraepithelial neoplasia (IEN)

KW - Lung cancer

KW - Risk assessment

UR - http://www.scopus.com/inward/record.url?scp=84859976811&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859976811&partnerID=8YFLogxK

U2 - 10.3233/ACP-2012-0053

DO - 10.3233/ACP-2012-0053

M3 - Article

C2 - 22277916

AN - SCOPUS:84859976811

VL - 35

SP - 187

EP - 201

JO - Analytical Cellular Pathology

JF - Analytical Cellular Pathology

SN - 2210-7177

IS - 3

ER -