Sputum examination for early detection of lung cancer

Conventional sputum cytology can be used for the detection of lung cancer, but has shown a low yield in prospective screening trials. This review focuses on the technical aspects relevant to the outcome of DNA and image analysis in sputum. Published articles are discussed in the light of the technical background. Recent developments in DNA analysis and nuclear image analysis show a clear potential to improve or refine diagnosis beyond that achieved with conventional sputum cytology examination. The challenge for future studies in DNA and nuclear analysis of sputum is to ensure high levels of quality control and to confirm these initial encouraging results.

[1]  E. Smit,et al.  Outcome of bronchial carcinoma in situ. , 2000, Chest.

[2]  W. Franklin,et al.  Examination of p53 alterations and cytokeratin expression in sputa collected from patients prior to histological diagnosis of squamous cell carcinoma , 1996, Journal of cellular biochemistry. Supplement.

[3]  C. Carpenter,et al.  DNA methylation analysis: a powerful new tool for lung cancer diagnosis , 2002, Oncogene.

[4]  Z. Ronai,et al.  High frequency of K‐ras mutations in normal appearing lung tissues and sputum of patients with lung cancer , 1995, International journal of cancer.

[5]  T. Zhukov,et al.  Prospective detection of preclinical lung cancer: results from two studies of heterogeneous nuclear ribonucleoprotein A2/B1 overexpression. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[6]  Chih-Yi Chen,et al.  Alterations of the p16ink4a gene in resected nonsmall cell lung tumors and exfoliated cells within sputum , 2002, International journal of cancer.

[7]  D. Conte,et al.  Molecular changes track recurrence and progression of bronchial precancerous lesions. , 2002, Lung cancer.

[8]  F. Gilliland,et al.  Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers. , 2002, Cancer research.

[9]  B Palcic,et al.  Sputum screening by quantitative microscopy: a reexamination of a portion of the National Cancer Institute Cooperative Early Lung Cancer Study. , 1997, Mayo Clinic proceedings.

[10]  Christoph Grunau,et al.  Bisulfite genomic sequencing: systematic investigation of critical experimental parameters , 2001, Nucleic Acids Res..

[11]  M. Tockman,et al.  A case-cohort study of an early biomarker of lung cancer in a screening cohort of Yunnan tin miners in China. , 1997, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[12]  M. von Knebel Doeberitz,et al.  Sensitive detection of rare cancer cells in sputum and peripheral blood samples of patients with lung cancer by preproGRP‐specific RT‐PCR , 2001, International journal of cancer.

[13]  Y. Miller,et al.  Cytopathological analysis of sputum in patients with airflow obstruction and significant smoking histories. , 1996, Cancer research.

[14]  I O Ellis,et al.  Interlaboratory comparison of DNA image analysis. , 1996, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[15]  J. Verdebout,et al.  Expression of p53 in preneoplastic and early neoplastic bronchial lesions. , 2002, Oncology reports.

[16]  G. Sorenson,et al.  Analysis of the allele-specific PCR method for the detection of neoplastic disease. , 1997, Diagnostic molecular pathology : the American journal of surgical pathology, part B.

[17]  E. Bossen,et al.  Ten years of respiratory cytopathology at Duke University Medical Center. II. The cytopathologic diagnosis of lung cancer during the years 1970 to 1974, with a comparison between cytopathology and histopathology in the typing of lung cancer. , 1981, Acta cytologica.

[18]  G. Bepler,et al.  Screening for lung cancer. , 2000, The New England journal of medicine.

[19]  Ng Ab,et al.  Factors significant in the diagnostic accuracy of lung cytology in bronchial washing and sputum samples. II. Sputum samples. , 1983 .

[20]  R. Hruban,et al.  Detection of oncogene mutations in sputum precedes diagnosis of lung cancer. , 1994, Cancer research.

[21]  J. E. Boers,et al.  P53 in squamous metaplasia: a marker for risk of respiratory tract carcinoma. , 1996, American journal of respiratory and critical care medicine.

[22]  Rolando Estrada,et al.  Application of cell‐image analysis to the diagnosis of cellular atypias in sputum: A review , 1986, Diagnostic cytopathology.

[23]  M. Spitz,et al.  Consensus statements from the Second International Lung Cancer Molecular Biomarkers Workshop: a European strategy for developing lung cancer molecular diagnostics in high risk populations. , 2002, International journal of oncology.

[24]  T. Topalidis,et al.  Can semi-automated image cytometry on induced sputum become a screening tool for lung cancer? , 2001, European Respiratory Journal.

[25]  U. Pastorino,et al.  Microsatellite alterations in bronchial and sputum specimens of lung cancer patients. , 1996, Cancer research.

[26]  G. Byrnes,et al.  Screening for lung cancer. , 2004, The Cochrane database of systematic reviews.

[27]  E. Wouters,et al.  Applicability of induced sputum for molecular dosimetry of exposure to inhalatory carcinogens: 32P-postlabeling of lipophilic DNA adducts in smokers and nonsmokers. , 2000, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[28]  A. Kraus,et al.  Differential frequencies of p16(INK4a) promoter hypermethylation, p53 mutation, and K-ras mutation in exfoliative material mark the development of lung cancer in symptomatic chronic smokers. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  E Gabrielson,et al.  Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Hironobu Ohmatsu,et al.  Screening for lung cancer with low-dose helical computed tomography: anti-lung cancer association project. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  H. Kato,et al.  K-ras mutation in sputum of primary lung cancer patients does not always reflect that of cancerous cells. , 2001, International journal of oncology.

[32]  G. Swan,et al.  Discriminant analysis of lower respiratory tract components associated with cigarette smoking, based on quantitative sputum cytology. , 1990, Acta cytologica.

[33]  N. Arnheim,et al.  Extension of base mispairs by Taq DNA polymerase: implications for single nucleotide discrimination in PCR. , 1992, Nucleic acids research.

[34]  P. Pairolero,et al.  Roentgenographically occult lung cancer: pathologic findings and frequency of multicentricity during a 10-year period. , 1984, Mayo Clinic proceedings.

[35]  C. Kortsik,et al.  Comparison of the sensitivity of sputum and brush cytology in the diagnosis of lung carcinomas. , 1997, Acta cytologica.

[36]  J. Herman,et al.  Predicting lung cancer by detecting aberrant promoter methylation in sputum. , 2000, Cancer research.

[37]  W. C. Ball,et al.  Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Johns Hopkins study. , 2015, The American review of respiratory disease.

[38]  I. Wistuba,et al.  Smoking molecular damage in bronchial epithelium , 2002, Oncogene.

[39]  Y. Miller,et al.  Screening for lung cancer revisited and the role of sputum cytology and fluorescence bronchoscopy in a high-risk group. , 2000, Chest.

[40]  K. Omoe,et al.  K-ras gene mutation in sputum samples containing atypical cells and adenocarcinoma cells in the lung. , 1996, Carcinogenesis.

[41]  V. Somers,et al.  Detection of K-ras point mutations in sputum from patients with adenocarcinoma of the lung by point-EXACCT. , 2003, Methods in molecular medicine.

[42]  T. Petty,et al.  Outcome of 51 patients with roentgenographically occult lung cancer detected by sputum cytologic testing: a community hospital program. , 1994, Archives of internal medicine.

[43]  Calum MacAulay,et al.  Increase of sensitivity of sputum cytology using high-resolution image cytometry: field study results. , 2002, Cytometry.

[44]  H. Fujiki,et al.  Heterogeneous nuclear ribonucleoprotein B1 as a new marker of early detection for human lung cancers. , 1999, Cancer research.

[45]  A. Neubauer,et al.  Facilitated detection of oncogene mutations from exfoliated tissue material by a PNA‐mediated ‘enriched PCR’ protocol , 2000, The Journal of pathology.

[46]  F. Gilliland,et al.  Glutathione S-transferase P1 and NADPH quinone oxidoreductase polymorphisms are associated with aberrant promoter methylation of P16(INK4a) and O(6)-methylguanine-DNA methyltransferase in sputum. , 2002, Cancer research.

[47]  A. Ambergen,et al.  Validation of the Point-EXACCT method in non-small cell lung carcinomas. , 1998, Clinical chemistry.

[48]  A. Ng,et al.  Factors significant in the diagnostic accuracy of lung cytology in bronchial washing and sputum samples. II. Sputum samples. , 1983, Acta Cytologica.

[49]  Risse Ek,et al.  Relationship between patient characteristics and the sputum cytologic diagnosis of lung cancer. , 1987 .

[50]  Manel Esteller,et al.  DNA methylation: a profile of methods and applications. , 2002, BioTechniques.

[51]  M. Tockman.  Advances in sputum analysis for screening and early detection of lung cancer. , 2000, Cancer control : journal of the Moffitt Cancer Center.

[52]  Detection of p53 mutations in sputum smears precedes diagnosis of non-small cell lung carcinoma. , 2000, Anticancer research.

[53]  C. Ford.  Prospective Detection of Preclinical Lung Cancer : Results from Two Studies of Heterogeneous Nuclear Ribonucleoprotein A 2 / B 1 Overexpression , 2000 .

[54]  Marshall W. Anderson,et al.  Genetic markers for early detection of lung cancer and outcome measures for response to chemoprevention , 1997, Journal of cellular biochemistry. Supplement.

[55]  L. Thiberville,et al.  Follow-up of bronchial precancerous lesions and carcinoma in situ using fluorescence endoscopy. , 2001, American journal of respiratory and critical care medicine.

[56]  T. Petty,et al.  Diagnosis of roentgenographically occult lung cancer by sputum cytology. , 2002, Clinics in chest medicine.

[57]  D. Sugarbaker,et al.  Chest X-ray screening improves outcome in lung cancer. A reappraisal of randomized trials on lung cancer screening. , 1995, Chest.

[58]  H. Fujiki,et al.  Heterogeneous nuclear ribonucleoprotein B1 as early cancer biomarker for occult cancer of human lungs and bronchial dysplasia. , 2001, Cancer research.

[59]  G. Swan,et al.  Quantitative sputum cytologic findings in 109 nonsmokers. , 1989, The American review of respiratory disease.

[60]  C. Agustí,et al.  Induced sputum in the diagnosis of peripheral lung cancer not visible endoscopically. , 2001, Respiratory medicine.

[61]  G. Schumann,et al.  Sputum cytology. , 1979, American family physician.

[62]  W Schaafsma,et al.  Further evaluation of quantitative nuclear image features for classification of lung carcinomas. , 1992, Pathology, research and practice.

[63]  E. C. Hammond,et al.  Changes in bronchial epithelium in relation to cigarette smoking, 1955-1960 vs. 1970-1977. , 1979, The New England journal of medicine.

[64]  J. Braman,et al.  PCR fidelity of pfu DNA polymerase and other thermostable DNA polymerases. , 1996, Nucleic acids research.

[65]  O. Auerbach,et al.  Development of carcinoma of the lung as reflected in exfoliated cells , 1974, Cancer.

[66]  A. Gazdar,et al.  Early detection of lung cancer: clinical perspectives of recent advances in biology and radiology. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[67]  M. V. van’t Hof,et al.  Sputum cytology by the saccomanno method in diagnosing lung malignancy , 1985, Diagnostic cytopathology.

[68]  T. Petty,et al.  Efficacy of Two Sputum Collection Techniques in Patients with Air Flow Obstruction , 1999, Acta Cytologica.

[69]  Anthony B. Miller,et al.  Lung Cancer Screening , 1986 .

[70]  Y. Miller,et al.  Molecular events in lung carcinogenesis. , 1997, Hematology/oncology clinics of North America.

[71]  J. Minna,et al.  Promoter methylation and silencing of the retinoic acid receptor-beta gene in lung carcinomas. , 2001, Journal of the National Cancer Institute.