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Immunohistochemical staining and computed tomography in early detection of lung cancer among heavy smokers: A pilot study

Abstract

Objectives

Early diagnosis of lung cancer carries a good prognosis. The aim of the present study was early detection of lung cancer among heavy smokers using immunohistochemical staining and chest computed tomography (CT).

Patients and methods

This descriptive cross-sectional study comprised 80 heavy smokers with smoking index more than 40 pack-years. They were recruited from the Smoking Cessation Clinic, Mansoura University Hospital. All participants were subjected to (a) chest radiography followed by high-resolution chest CT, (b) sputum sample collection, and (c) fiberoptic bronchoscopy evaluation of bronchoalveolar lavage (BAL) and bronchial mucosal biopsies from suspicious areas. All pathological samples were stained with hematoxylin and eosin followed by immunostaining using antibodies for p53 and thyroid transcription factor-1 (TTF-1). Data were analyzed using statistical package for social sciences, version 16.

Results

The majority of heavy smokers were male, withamean age of 53.42±11.30 years. A solitary pulmonary nodule was detectedin1.3%of cases withchest radiographyandin5%with high-resolution CT. Hematoxylin and eosin staining of sputum, BAL, and mucosal biopsies was positive for premalignant changes in 35, 27, and 17.56%of cases, respectively. Sputum, BAL, and mucosal biopsies showed expression of p53 in 30, 37.8, and 35.1% of cases, respectively. Sputum, BAL, and mucosal biopsy showed expression of TTF-1 in 12.5, 10.8, and 14.9% of cases, respectively.

Conclusion

The immunohistochemical technique using p53 and TTF-1 is useful in the early detection of bronchial mucosal changes in heavy smokers. There is still need for a largescale study to highlight its validity and acceptability. Meanwhile, chest CT is beneficial for the detection of peripheral small lesions.

References

  1. World Health Organization (WHO) Regional Office for the Eastern Mediterranean. Report on Global Adult Tobacco Survey (GATS), Egypt; 2009. Available at: http://www.who.int/tobacco/surveillance/ gats_rep_egypt.pdf?ua=1.

  2. Cornfield J, Haenszel W, Hammond E, Lilienfeld A, Shimkin M, et al. Smoking and lung cancer: recent evidence and a discussion of some questions. Int J Epidemiol 2009; 38:1175–1191.

    Article  Google Scholar 

  3. Van Klaveren RJ. Is CT screening for lung cancer ready for prime time? J Thorac Imaging 2011; 26:4–6.

    Article  Google Scholar 

  4. Jemal A, Siegel R, Ward E. Cancer statistics. CA Cancer J Clin 2006; 56:106–130.

    Article  Google Scholar 

  5. Ponticiello A, Barra E, Giani U. P53 immunohistochemistry can identify bronchial dysplastic lesions proceeding to lung cancer: a prospective study. Eur Respir J 2004; 15:547–552.

    Article  Google Scholar 

  6. Fan YG, HU P, Jiang Y, Chang RS, Yao SX, Wang W, et al. Association between sputum atypia and lung cancer risk in an occupational cohort in Yunnan, China. Chest 2009; 3:778–785.

    Article  Google Scholar 

  7. Moldvay J, Jackel M, Bogos K, Soltez I, Agoes L. The role of TTF-1 in differentiating primary and metastatic lung adenocarcinoma. Pathol Oncol Res 2004; 2:85–88.

    Article  Google Scholar 

  8. Byers T, Wolf HJ, Franklin WA, Braudrick S, Merrick DT, Shroyer KR, et al. Sputum cytologic atypia predicts incidence lung cancer defining latency and histologic specificity. Cancer Epidemiol Biomarkers Prev 2008; 17:158–162.

    CAS  Article  Google Scholar 

  9. National Cancer Institute. Definition of pack year. Available at: http://www. cancer.gov/dictionary?CdrID=306510.

  10. Myong NH. Thyroid transcription factor-1 (TTF-1) expression in human lung carcinomas: its prognostic implication and relationship with expressions of P53 ki-67 proteins. J Korean Med Sci 2003; 4:494–500.

    Article  Google Scholar 

  11. Mitsudomi T, Yatube Y, Takahashi T. TTF-1 expression in pulmonary adenocarcinomas. Am J Surg Pathol 2002; 26:767–773.

    Article  Google Scholar 

  12. Corner J, Hopkinson J, Fitzsimmons D, Barclay S, Muers M. Is late diagnosis of lung cancer inevitable? Interview study of patients’ recollections of symptoms before diagnosis. Thorax 2005; 60:314–319.

    CAS  Article  Google Scholar 

  13. Agaku IT, King BA, Dube SR. Current cigarette smoking among adults − United States, 2005–2012. Morb Mortal Wkly Rep 2014; 2:29–34.

    Google Scholar 

  14. Gaworski CL, Dozier MM, Eldridge SR, Morrisey R, Rajendran N, Gerhart JM. Cigarette smoke vapor-phase effects in the rat upper respiratory tract. Inhal Toxicol 1998; 10:857–873.

    CAS  Article  Google Scholar 

  15. Sethi S. COPD X-ray changes. Indian J Radiol 2004; 18:122–128.

    Google Scholar 

  16. National Lung Screening Trial Research Team, Church TR, Black WC, Aberle DR, Berg CD, Clingan KL, Duan F, et al. Results of initial low- dose computed tomographic screening for lung cancer. N Engl J Med 2013; 368:1980–1991.

    Article  Google Scholar 

  17. Swensen SJ, Jell JR, Hartman TE, Midthun DE, Sloan JA, Sykes AM, Aughenbaugh GL, et al. Lung cancer screening with CT. Mayo Clinic Experience. Radiology 2003; 113:25–45.

    Google Scholar 

  18. Becker N, Motsch E, Gross ML, Eigentopf A, Heussel CP, Dienemann H, et al. Randomized study on early detection of lung cancer with MSCT in Germany: study design and results of the first screening round. J Cancer Res Clin Oncol 2012; 9:1475–1486.

    Article  Google Scholar 

  19. Estarriol MH, Godoy MR, Sanchez MV, Sot MTC. Bronchoscopic lung biopsy with fluoroscopy to study 164 localized pulmonary lesions. Arch Bronconeumol 2004; 40:483–488.

    Google Scholar 

  20. Fuso L, Pagliari G, Boniello V, Trove A, Varone F. Autofluorescence bronchoscopy to identify precancerous bronchial lesions. Monaldi Arch Chest Dis 2005; 3:124–128.

    Google Scholar 

  21. Gregory L, Nachimuthu N, Tan D, Enriqueta N, Martin M, et al. Autofluorescence bronchoscopy of lung cancer surveillance based on risk assessment. Chest 2007; 4:335–340.

    Google Scholar 

  22. Seok D, Chul K, Hyun D, Yong IL, Young W, Koo S, et al. Clinical implication of atypical cells from sputum in patients without lung cancer. Respirology 2006; 44:462–466.

    Google Scholar 

  23. Nicholson AG, Perry LJ, Cury OM, Jackson P, McCormick CM, Corrin B, et al. Reproducibility of the WHO/IASLC grading system for pre-invasive squamous lesions of the bronchus: a study of inter-observer and intraobserver variation. Histopathology 2001; 38:202–208.

    CAS  Article  Google Scholar 

  24. Chandrika J, Piyathilake BPS, Andro A, Heidi W, Douglas C. Nuclear accumulation of p53 is potential marker for development of squamous cell lung cancer in smokers. Cancer 2003; 93:330–336.

    Google Scholar 

  25. Feng Z, Tian D, Lan Q, Mumford J. A sensitive immunofluorescence assay for detection of p53 protein accumulation in sputum. Anticancer Res 1999; 9:3847–3852.

    Google Scholar 

  26. Keohavong PH, Lan Q, Gao W, Zheng K, Mady H, Methem M, Mamford J. Detection of p53 and R-ras mutations in sputum of individuals exposed to smoky coal emission in Xu and Wei country. China Carcinogenesis 2005; 2:303–308.

    Google Scholar 

  27. Bennett WP, Alvanja MC, Blomeke B. Environmental tobacco smoke, genetic susceptibility, and risk of lung cancer in never-smoking women. J Natl Cancer Inst 1999; 91:2009–2014.

    CAS  Article  Google Scholar 

  28. Walker C, Robertson J, Myskow W, Pendleton N, Dixon G. p53 expression in normal and dysplastic bronchial epithelium and in lung carcinoma. Br J Cancer 1994; 2:297–303.

    Article  Google Scholar 

  29. Kalomenidis J, Orfanidou D, Rasidakis A, Papamichalls G, Toumbis M, Labaditis J, et al. Immunohistochemical detection of p53 protein in neoplastic, preneoplastic and normal bronchial mucosa specimens obtained during diagnostic bronchoscopy. Oncol Rep 1998; 3:763–769.

    Google Scholar 

  30. El-Gammal M, Nafee R, Ghoneim A, Abd El-Salam H, Ramadan M. p53 gene mutations in lung cancer patients. Egypt J Chest Dis 2003; 2:237–250.

    Google Scholar 

  31. Nanguzgambo AB, Razack R, Louw M, Bolliger CT. Immunochemistry and lung cancer: application in diagnosis, prognosis and targeted therapy. Oncology 2011; 80:247–256.

    CAS  Article  Google Scholar 

  32. Stenhouse G, Fyfe N, King G, Chapman A, Kerr KM. Thyroid transcription factor- 1 in pulmonary adenocarcinoma. J Clin Pathol 2004; 4:383–387.

    Article  Google Scholar 

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Correspondence to Nesrien M. Shalabi MD.

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Shalabi, N.M., El-Badrawy, M.K., El-Morsy, A.S. et al. Immunohistochemical staining and computed tomography in early detection of lung cancer among heavy smokers: A pilot study. Egypt J Bronchol 11, 149–153 (2017). https://doi.org/10.4103/1687-8426.203800

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  • DOI: https://doi.org/10.4103/1687-8426.203800

Keywords

  • chest computed tomography
  • lung cancer screening
  • lung cancer
  • monoclonal antibody p53
  • protein p53
  • sputum cytology
  • thyroid transcription factor-1