Applications of Molecular Tests in Anatomic Pathology

  • Jennifer L. Hunt
  • Sanja Dacic
Part of the Molecular Pathology Library book series (MPLB, volume 1)


Molecular testing in anatomic pathology is becoming increasingly important for most organ systems, including in the lung. Such tests are used both diagnostically and prognostically and are particularly important in the workup of neoplasia and for identification or subclassification for certain infectious processes. Fresh and frozen tissues are always considered to be the most optimal source of DNA and RNA that serves as the template for targeted molecular analysis. However, archival paraffin-embedded tissue is an attractive alternative source of tissue for clinical testing. Paraffin-embedded tissue can be a critical source of nucleic acid when unexpected diagnoses are rendered in the pathologic evaluation of tissue material. It also, however, provides the advantage of allowing for archival analysis with correlation to outcome.


Epidermal Growth Factor Receptor Comparative Genomic Hybridization Epidermal Growth Factor Receptor Mutation KRAS Mutation Small Cell Carcinoma 
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  1. 1.
    Hunt JL, Finkelstein SD. Microdissection techniques for molecular testing in surgical pathology. Arch Pathol Lab Med 2004;128:1372–1378.PubMedGoogle Scholar
  2. 2.
    Eltoum IA, Siegal GP, Frost AR. Microdissection of histologic sections: past, present, and future. Adv Anat Pathol 2002;9:316–322.CrossRefPubMedGoogle Scholar
  3. 3.
    Simone NL, Paweletz CP, Charboneau L, et al. Laser capture microdissection: beyond functional genomics to proteomics. Mol Diagnosis 2000;5:301–307.Google Scholar
  4. 4.
    Rodenhuis S, Slebos RJ. The ras oncogenes in human lung cancer. Am Rev Respir Dis 1990;142:S27–S30.PubMedGoogle Scholar
  5. 5.
    Westra WH, Slebos RJ, Offerhaus GJ, et al. K-ras oncogene activation in lung adenocarcinomas from former smokers. Evidence that K-ras mutations are an early and irreversible event in the development of adenocarcinoma of the lung. Cancer 1993;72:432–438.CrossRefPubMedGoogle Scholar
  6. 6.
    Nelson HH, Christiani DC, Mark EJ, et al. Implications and prognostic value of K-ras mutation for early-stage lung cancer in women. J Natl Cancer Inst 1999;91:2032–2038.CrossRefPubMedGoogle Scholar
  7. 7.
    Chapman AD, Kerr KM. The association between atypical adenomatous hyperplasia and primary lung cancer. Br J Cancer 2000;83:632–636.CrossRefPubMedGoogle Scholar
  8. 8.
    Mao L, Hruban RH, Boyle JO, et al. Detection of oncogene mutations in sputum precedes diagnosis of lung cancer. Cancer Res 1994;54:1634–1637.PubMedGoogle Scholar
  9. 9.
    Ronai Z, Yabubovskaya MS, Zhang E, et al. K-ras mutation in sputum of patients with or without lung cancer. J Cell Biochem Suppl 1996;25:172–176.CrossRefPubMedGoogle Scholar
  10. 10.
    Nakajima E, Hirano T, Konaka C, et al. K-ras mutation in sputum of primary lung cancer patients does not always reflect that of cancerous cells. Int J Oncol 2001;18:105–110.PubMedGoogle Scholar
  11. 11.
    Destro A, Bianchi P, Alloisio M, et al. K-ras and p16(INK4A)alterations in sputum of NSCLC patients and in heavy asymptomatic chronic smokers. Lung Cancer 2004;44:23–32.CrossRefPubMedGoogle Scholar
  12. 12.
    Wistuba II, Behrens C, Milchgrub S, et al. Sequential molecular abnormalities are involved in the multistage development of squamous cell lung carcinoma. Oncogene 1999;18:643–650.CrossRefPubMedGoogle Scholar
  13. 13.
    Wistuba II, Lam S, Behrens C, et al. Molecular damage in the bronchial epithelium of current and former smokers. J Natl Cancer Inst 1997;89:1366–1373.CrossRefPubMedGoogle Scholar
  14. 14.
    Wistuba II, Behrens C, Virmani AK, et al. High resolution chromosome 3p allelotyping of human lung cancer and preneoplastic/preinvasive bronchial epithelium reveals multiple, discontinuous sites of 3p allele loss and three regions of frequent breakpoints. Cancer Res 2000;60:1949–1960.PubMedGoogle Scholar
  15. 15.
    Nakamura H, Kawasaki N, Taguchi M, et al. Survival impact of epidermal growth factor receptor overexpression in patients with non-small cell lung cancer: a meta-analysis. Thorax 2006;61:140–145.CrossRefPubMedGoogle Scholar
  16. 16.
    Suzuki S, Dobashi Y, Sakurai H, et al. Protein overexpression and gene amplification of epidermal growth factor receptor in nonsmall cell lung carcinomas. An immunohistochemical and fluorescence in situ hybridization study. Cancer 2005;103:1265–1273.CrossRefPubMedGoogle Scholar
  17. 17.
    Hirsch FR, Varella-Garcia M, Bunn PA Jr, et al. Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol 2003;21:3798–3807.CrossRefPubMedGoogle Scholar
  18. 18.
    Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129–2139.CrossRefPubMedGoogle Scholar
  19. 19.
    Nagahara H, Mimori K, Ohta M, et al. Somatic mutations of epidermal growth factor receptor in colorectal carcinoma. Clin Cancer Res 2005;11:1368–1371.CrossRefPubMedGoogle Scholar
  20. 20.
    Lee JW, Soung YH, Kim SY, et al. Somatic mutations of EGFR gene in squamous cell carcinoma of the head and neck. Clin Cancer Res 2005;11:2879–2882.CrossRefPubMedGoogle Scholar
  21. 21.
    Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497–1500.CrossRefPubMedGoogle Scholar
  22. 22.
    Cappuzzo F, Hirsch FR, Rossi E, et al. Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst 2005;97:643–655.PubMedCrossRefGoogle Scholar
  23. 23.
    Johansen IS, Thomsen VO, Forsgren A, et al. Detection of Mycobacterium tuberculosis complex in formalin-fixed, paraffin-embedded tissue specimens with necrotizing granulomatous inflammation by strand displacement amplification. J Mol Diagn 2004;6:231–236.PubMedGoogle Scholar
  24. 24.
    Marchetti G, Gori A, Catozzi L, et al. Evaluation of PCR in detection of Mycobacterium tuberculosis from formalinfixed, paraffin-embedded tissues: comparison of four amplification assays. J Clin Microbiol 1998;6:1512–1517.Google Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Jennifer L. Hunt
    • 1
  • Sanja Dacic
    • 2
  1. 1.AP Molecular Diagnostics Unit, Department of Anatomic PathologyCleveland ClinicClevelandUSA
  2. 2.Department of PathologyUniversity of Pittsburgh Medical CenterPittsburghUSA

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