Journal of Clinical Oncology, Vol 6, 1685-1693, Copyright © 1988 by American Society of Clinical Oncology

ARTICLES

Sensitive and specific monoclonal antibody recognition of human lung cancer antigen on preserved sputum cells: a new approach to early lung cancer detection

MS Tockman, PK Gupta, JD Myers, JK Frost, SB Baylin, EB Gold, AM Chase, PH Wilkinson and JL Mulshine
Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205.

Murine monoclonal antibodies (Mabs) to a glycolipid antigen of small- cell (SCC) and a protein antigen of non-small-cell lung cancer (NSCC) were applied to preserved sputum specimens from individuals who participated in The Johns Hopkins Lung Project (JHLP). In that study, undertaken in 1973 to evaluate the efficacy of sputum cytology screening, half of the high-risk participants (5,226 men, greater than or equal to 45 years of age, currently smoking greater than or equal to 1 pack of cigarettes per day) were randomly assigned to produce specimens for cytopathological analysis. During regular screenings over the next 5 to 8 years, 626 (12%) showed moderate (or greater) atypia. Sixty-nine of these (26 who progressed to cancer, 43 who did not) were randomly selected for a blinded improved Mab immunostaining protocol in the present study. Satisfactory specimens with morphologic atypia immunostained positively in 14 of the 22 patients who eventually progressed to cancer (sensitivity 64%), and were nonreactive in 35 of the 40 patients who did not progress to lung cancer (specificity 88%). Review of the true positive specimens (14/22 atypias) showed that they were collected 24 months in advance of diagnosis. In contrast, the 8/22 false negative atypias (failure to stain) showed that they were collected for an average of 57 months preceding the diagnosis of cancer. Subsequent specimens (average, 26 months before cancer) from participants who were originally considered "false negative" did stain positively improving sensitivity to 91% among specimens collected for an average of 2 years in advance of the clinical appearance of lung cancer. Specificity remained at 88%. Recognition of neoplastic antigen expression 2 years in advance of clinical cancer may be a valuable intermediate end point in studies of lung cancer prevention, detection, and therapy.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				Y.-G. Fan, P. Hu, Y. Jiang, R.-S. Chang, S.-X. Yao, W. Wang, J. He, P. Prorok, and Y.-L. Qiao Association Between Sputum Atypia and Lung Cancer Risk in an Occupational Cohort in Yunnan, China Chest, March 1, 2009; 135(3): 778 - 785. [Abstract] [Full Text] [PDF]

				J. Chen, S. Lam, A. Pilon, A. McWilliams, C. MacAulay, and E. Szabo Higher Levels of the Anti-inflammatory Protein CC10 Are Associated with Improvement in Bronchial Dysplasia and Sputum Cytometric Assessment in Individuals at High Risk for Lung Cancer Clin. Cancer Res., March 1, 2008; 14(5): 1590 - 1597. [Abstract] [Full Text] [PDF]

				G. J. Kelloff, S. M. Lippman, A. J. Dannenberg, C. C. Sigman, H. L. Pearce, B. J. Reid, E. Szabo, V. C. Jordan, M. R. Spitz, G. B. Mills, et al. Progress in Chemoprevention Drug Development: The Promise of Molecular Biomarkers for Prevention of Intraepithelial Neoplasia and Cancer--A Plan to Move Forward Clin. Cancer Res., June 15, 2006; 12(12): 3661 - 3697. [Abstract] [Full Text] [PDF]

				A. K. Ganti and J. L. Mulshine Lung cancer screening. Oncologist, May 1, 2006; 11(5): 481 - 487. [Abstract] [Full Text] [PDF]

				S S Birring and M D Peake Symptoms and the early diagnosis of lung cancer Thorax, April 1, 2005; 60(4): 268 - 269. [Full Text] [PDF]

				L. L. Humphrey, S. Teutsch, and M. Johnson Lung Cancer Screening with Sputum Cytologic Examination, Chest Radiography, and Computed Tomography: An Update for the U.S. Preventive Services Task Force Ann Intern Med, May 4, 2004; 140(9): 740 - 753. [Abstract] [Full Text] [PDF]

				A. McWilliams, J. Mayo, S. MacDonald, J. C. leRiche, B. Palcic, E. Szabo, and S. Lam Lung Cancer Screening: A Different Paradigm Am. J. Respir. Crit. Care Med., November 15, 2003; 168(10): 1167 - 1173. [Abstract] [Full Text] [PDF]

				S. A. Prindiville, T. Byers, F. R. Hirsch, W. A. Franklin, Y. E. Miller, K. O. Vu, H. J. Wolf, A. E. Baron, K. R. Shroyer, C. Zeng, et al. Sputum Cytological Atypia as a Predictor of Incident Lung Cancer in a Cohort of Heavy Smokers with Airflow Obstruction Cancer Epidemiol. Biomarkers Prev., October 1, 2003; 12(10): 987 - 993. [Abstract] [Full Text] [PDF]

				J. Deslauriers Should screening for lung cancer be revisited? J. Thorac. Cardiovasc. Surg., March 1, 2003; 125(90030): S94 - 95. [Full Text] [PDF]

				M. Garayoa, Y.-G. Man, A. Martinez, F. Cuttitta, and J. L. Mulshine Downregulation of hnRNP A2/B1 Expression in Tumor Cells under Prolonged Hypoxia Am. J. Respir. Cell Mol. Biol., January 1, 2003; 28(1): 80 - 85. [Abstract] [Full Text] [PDF]

				S. G. Spiro and J. C. Porter Lung Cancer--Where Are We Today?: Current Advances in Staging and Nonsurgical Treatment Am. J. Respir. Crit. Care Med., November 1, 2002; 166(9): 1166 - 1196. [Abstract] [Full Text] [PDF]

				K. Garg, R. L. Keith, T. Byers, K. Kelly, A. L. Kerzner, D. A. Lynch, and Y. E. Miller Randomized Controlled Trial with Low-Dose Spiral CT for Lung Cancer Screening: Feasibility Study and Preliminary Results Radiology, November 1, 2002; 225(2): 506 - 510. [Abstract] [Full Text] [PDF]

				F.R. Hirsch, D.T. Merrick, and W.A. Franklin Role of biomarkers for early detection of lung cancer and chemoprevention Eur. Respir. J., June 1, 2002; 19(6): 1151 - 1158. [Abstract] [Full Text] [PDF]

				W. Marek, N. Kotschy-Lang, A. Muti, Ch. Kohler, L. Nielsen, Th. Topalidis, Z. Atay, and J.A. Nakhosteen Can semi-automated image cytometry on induced sputum become a screening tool for lung cancer?: Evaluation of quantitative semi-automated sputum cytometry on radon- and uranium-exposed workers Eur. Respir. J., December 1, 2001; 18(6): 942 - 950. [Abstract] [Full Text] [PDF]

				W. D. BENNETT, K. L. ZEMAN, C. FOY, C. L. SHAFFER, F. L. JOHNSON, J. A. REGNIS, A. SANNUTI, and J. JOHNSON Effect of Aerosolized Uridine 5'-Triphosphate on Mucociliary Clearance in Mild Chronic Bronchitis Am. J. Respir. Crit. Care Med., July 15, 2001; 164(2): 302 - 306. [Abstract] [Full Text] [PDF]

				J. Deslauriers Should screening for lung cancer be revisited? J. Thorac. Cardiovasc. Surg., June 1, 2001; 121(6): 1031 - 1032. [Full Text] [PDF]

				E. Sueoka, N. Sueoka, Y. Goto, S. Matsuyama, H. Nishimura, M. Sato, S. Fujimura, H. Chiba, and H. Fujiki Heterogeneous Nuclear Ribonucleoprotein B1 as Early Cancer Biomarker for Occult Cancer of Human Lungs and Bronchial Dysplasia Cancer Res., March 1, 2001; 61(5): 1896 - 1902. [Abstract] [Full Text]

				F. R. Hirsch, W. A. Franklin, A. F. Gazdar, and P. A. Bunn Jr. Early Detection of Lung Cancer: Clinical Perspectives of Recent Advances in Biology and Radiology Clin. Cancer Res., January 1, 2001; 7(1): 5 - 22. [Abstract] [Full Text]

				E. F. Patz, P. C. Goodman, and G. Bepler Screening for Lung Cancer N. Engl. J. Med., November 30, 2000; 343(22): 1627 - 1633. [Full Text] [PDF]

				Y.-G. Man, A. Martinez, I. M. Avis, S. H. Hong, F. Cuttitta, D. J. Venzon, and J. L. Mulshine Phenotypically Different Cells with Heterogeneous Nuclear Ribonucleoprotein A2/B1 Overexpression Show Similar Genetic Alterations Am. J. Respir. Cell Mol. Biol., November 1, 2000; 23(5): 636 - 645. [Abstract] [Full Text]

				T. L. Petty Screening Strategies for Early Detection of Lung Cancer: The Time Is Now JAMA, October 18, 2000; 284(15): 1977 - 1980. [Full Text] [PDF]

				W. N. ROM, J. G. HAY, T. C. LEE, Y. JIANG, and K.-M. TCHOU-WONG Molecular and Genetic Aspects of Lung Cancer Am. J. Respir. Crit. Care Med., April 1, 2000; 161(4): 1355 - 1367. [Full Text]

				C. M. Tammemagi, M. S. Tockman, J. L. Mulshine, and S. Piantadosi Correspondence re: M. S. Tockman et al., Prospective Detection of Preclinical Lung Cancer: Results from Two Studies of Heterogeneous Nuclear Ribonucleoprotein A2/B1 Overexpression. Clin. Cancer Res., 3: 2237-2246, 1997. Clin. Cancer Res., April 1, 2000; 6(4): 1601 - 1603. [Full Text]

				T. C. Kennedy, Y. Miller, and S. Prindiville Screening for Lung Cancer Revisited and the Role of Sputum Cytology and Fluorescence Bronchoscopy in a High-Risk Group Chest, April 1, 2000; 117(4_suppl_1): 72S - 79S. [Abstract] [Full Text] [PDF]

				J. Deslauriers and J. Gregoire Surgical Therapy of Early Non-Small Cell Lung Cancer Chest, April 1, 2000; 117(4_suppl_1): 104S - 109S. [Abstract] [Full Text] [PDF]

				T. L. Petty It's Time to Pick the Low-Hanging Fruit Chest, January 1, 2000; 117(1): 1 - 2. [Full Text] [PDF]

				P. Fielding, L. Turnbull, W. Prime, M. Walshaw, and J. K. Field Heterogeneous Nuclear Ribonucleoprotein A2/B1 Up-Regulation in Bronchial Lavage Specimens: A Clinical Marker of Early Lung Cancer Detection Clin. Cancer Res., December 1, 1999; 5(12): 4048 - 4052. [Abstract] [Full Text] [PDF]

				J. L. Mulshine Reducing Lung Cancer Risk* : Early Detection Chest, December 1, 1999; 116(suppl_3): 493S - 496S. [Abstract] [Full Text] [PDF]

				R. J. Michelson, M. W. Collard, A. J. Ziemba, J. Persinger, B. Bartholomew, and J. I. Huggenvik Nuclear DEAF-1-related (NUDR) Protein Contains a Novel DNA Binding Domain and Represses Transcription of the Heterogeneous Nuclear Ribonucleoprotein A2/B1 Promoter J. Biol. Chem., October 22, 1999; 274(43): 30510 - 30519. [Abstract] [Full Text] [PDF]

				E. Sueoka, Y. Goto, N. Sueoka, Y. Kai, T. Kozu, and H. Fujiki Heterogeneous Nuclear Ribonucleoprotein B1 as a New Marker of Early Detection for Human Lung Cancers Cancer Res., April 1, 1999; 59(7): 1404 - 1407. [Abstract] [Full Text] [PDF]

				P J M George Fluorescence bronchoscopy for the early detection of lung cancer Thorax, February 1, 1999; 54(2): 180 - 183. [Full Text]

				L. M. Montuenga, J. Zhou, I. Avis, M. Vos, A. Martinez, F. Cuttitta, A. M. Treston, M. Sunday, and J. L. Mulshine Expression of Heterogeneous Nuclear Ribonucleoprotein A2/B1 Changes with Critical Stages of Mammalian Lung Development Am. J. Respir. Cell Mol. Biol., October 1, 1998; 19(4): 554 - 562. [Abstract] [Full Text]

				T. L. Petty Is Prostate Cancer Screening Analogous to Lung Cancer Screening? JAMA, April 9, 1997; 277(14): 1120 - 1121. [Abstract] [PDF]

				K. S. Virgo, K. S. Naunheim, L. W. McKirgan, M. E. Kissling, J. C. Lin, and F. E. Johnson COST OF PATIENT FOLLOW-UP AFTER POTENTIALLY CURATIVE LUNG CANCER TREATMENT J. Thorac. Cardiovasc. Surg., August 1, 1996; 112(2): 356 - 363. [Abstract] [Full Text]

				J. Zhou, J. L. Mulshine, E. J. Unsworth, F. M. Scott, I. M. Avis, M. D. Vos, and A. M. Treston Purification and Characterization of a Protein That Permits Early Detection of Lung Cancer J. Biol. Chem., May 3, 1996; 271(18): 10760 - 10766. [Abstract] [Full Text] [PDF]

				K. E. Richert-Boe and L. L. Humphrey Screening for Cancers of the Lung and Colon Arch Intern Med, December 1, 1992; 152(12): 2398 - 2404. [Abstract] [PDF]

				T. L. Petty Pulmonary Medicine JAMA, May 16, 1990; 263(19): 2677 - 2678. [Abstract] [PDF]

				M. R. Melamed and B. J. Flehinger Screening for Lung Cancer Ann Intern Med, November 1, 1989; 111(9): 764 - 766. [Abstract] [PDF]