Copy number gains on 5p15, 6p11-q11, 7p12, and 8q24 are rare in sputum cells of individuals at high risk of lung cancer

Kettunen, Eeva; Salmenkivi, Kaisa; Vuopala, Katri; Toljamo, Tuula; Kuosma, Eeva; Norppa, Hannu; Knuutila, Sakari; Kaleva, Simo; Huuskonen, Matti S.; Anttila, Sisko

doi:10.1016/j.lungcan.2006.07.009

Cited by 17 publications

(19 citation statements)

References 24 publications

(41 reference statements)

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“…6,7 Other investigators tested epithelial cells in sputum by FISH using a commercial probe set for four different chromosomal regions (5p15, 6p11-q11, 7p12 (including epidermal growth factor receptor) and 8q24 (including C-myc), and required a positive sputum diagnosis to be based on DNA copy number gains for at least two probes in a minimum of two or three cells. 18,19 When using this approach, the sensitivity (50%) and specificity (81%) of FISH did not exceed the sensitivity of sputum cytology to detect lung cancer. 18 Furthermore, heavy tobacco smokers and asbestos-exposed workers had FISH results similar to those seen in never smokers, suggesting that the composition of these probes was not optimal for detecting early lung cancer in high-risk populations.…”

Section: Discussionmentioning

confidence: 92%

“…18,19 When using this approach, the sensitivity (50%) and specificity (81%) of FISH did not exceed the sensitivity of sputum cytology to detect lung cancer. 18 Furthermore, heavy tobacco smokers and asbestos-exposed workers had FISH results similar to those seen in never smokers, suggesting that the composition of these probes was not optimal for detecting early lung cancer in high-risk populations. 18 In contrast, others reported that FISH combined with cytology led to an improved diagnosis of malignancy.…”

Section: Discussionmentioning

confidence: 92%

“…18 Furthermore, heavy tobacco smokers and asbestos-exposed workers had FISH results similar to those seen in never smokers, suggesting that the composition of these probes was not optimal for detecting early lung cancer in high-risk populations. 18 In contrast, others reported that FISH combined with cytology led to an improved diagnosis of malignancy. 20 In a recent study, combined genetic aberrations for genes HYAL2 and FHIT were found with FISH in 76% of sputa from patients with cancer, but in only 47% of cases that considered positive on cytology, demonstrating that with an appropriate choice of probes, FISH can detect abnormal cells that may be undetectable by cytology.…”

Section: Discussionmentioning

confidence: 99%

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Automated detection of genetic abnormalities combined with cytology in sputum is a sensitive predictor of lung cancer

et al. 2008

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Detection of lung cancer by sputum cytology has low sensitivity but is noninvasive and, if improved, could be a powerful tool for early lung cancer detection. To evaluate whether the accuracy of diagnosing lung cancer by evaluating sputa for cytologic atypia and genetic abnormalities is greater than that of conventional cytology alone, automated scoring of genetic abnormalities for 3p22.1 and 10q22.3 (SP-A) by fluorescence in situ hybridization (FISH) and conventional cytology was done on sputa from 35 subjects with lung cancer, 25 high-risk smokers, and 6 healthy control subjects. Multivariate analysis was performed to select variables that most accurately predicted lung cancer. A model of probability for the presence of lung cancer was derived for each subject. Cells exfoliated from patients with lung cancer contained genetic aberrations and cytologic atypias at significantly higher levels than in those from control subjects. When combined with cytologic atypia, a model of risk for lung cancer was derived that had 74% sensitivity and 82% specificity to predict the presence of lung cancer, whereas conventional cytology achieved only 37% sensitivity and 87% specificity. For diagnosing lung cancer in sputum, a combination of molecular and cytologic variables was superior to using conventional cytology alone. Modern Pathology (2008) 21, 950-960;

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Automated detection of genetic abnormalities combined with cytology in sputum is a sensitive predictor of lung cancer

et al. 2008

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“…Using classical cytogenetic techniques, interphase fluorescence in situ hybridisation (FISH) and comparative genomic hybridisation (CGH), ~50% of NSCLC samples showed gains of chromosomes 6, 7 and 8 (27,28). Gains involving chromosome 5p are another frequent abnormality observed in NSCLC.…”

Section: Molecular Biology Of Lung Cancermentioning

confidence: 99%

Familial risk for lung cancer

2016

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Abstract. Lung cancer, which has a low survival rate, is a leading cause of cancer-associated mortality worldwide. Smoking and air pollution are the major causes of lung cancer; however, numerous studies have demonstrated that genetic factors also contribute to the development of lung cancer. A family history of lung cancer increases the risk for the disease in both smokers and never-smokers. This review focuses on familial lung cancer, in particular on the familial aggregation of lung cancer. The development of familial lung cancer involves shared environmental and genetic factors among family members. Familial lung cancer represents a good model for investigating the association between environmental and genetic factors, as well as for identifying susceptibility genes for lung cancer. In addition, studies on familial lung cancer may help to elucidate the etiology and mechanism of lung cancer, and may identify novel biomarkers for early detection and diagnosis, targeted therapy and improved prevention strategies. This review presents the aetiology and molecular biology of lung cancer and then systematically introduces and discusses several aspects of familial lung cancer, including the characteristics of familial lung cancer, population-based studies on familial lung cancer and the genetics of familial lung cancer.

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“…The LAVysion (Abbott Molecular, Des Plaines, Illinois) multicolor FISH probe 18 has been previously used for the early detection of lung cancer on cytological specimens. 11,[19][20][21][22][23][24][25][26] DNA-image cytometry uses the detection of DNA aneuploidy via an abnormal cellular DNA content after stoichiometric staining of DNA according to the Feulgen staining method. 27,28 Diagnostic application in pulmonary pathology has been reported for identification of prospective malignant lesions (ie, dysplasia) and prediction of prognosis in manifest cancers.…”

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confidence: 99%

Equivocal cytology in lung cancer diagnosis

Schramm

Wrobel

Born

et al. 2011

Cancer Cytopathology

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BACKGROUND:Sometimes, cytological lung cancer diagnosis is challenging because equivocal diagnoses are common. To enhance diagnostic accuracy, fluorescent in situ hybridization (FISH), DNA‐image cytometry, and quantitative promoter hypermethylation analysis have been proposed as adjuncts.METHODS:Bronchial washings and/or brushings or transbronchial fine‐needle aspiration biopsies were prospectively collected from patients who were clinically suspected of having lung carcinoma. After routine cytological diagnosis, 70 consecutive specimens, each cytologically diagnosed as negative, equivocal, or positive for cancer cells, were investigated with adjuvant methods. Suspicious areas on the smears were restained with the LAVysion multicolor FISH probe set (Abbott Molecular, Des Plaines, Illinois) or according to the Feulgen Staining Method for DNA‐image cytometry analysis. DNA was extracted from residual liquid material, and frequencies of aberrant methylation of APC, p16INK4A, and RASSF1A gene promoters were determined with quantitative methylation‐specific polymerase chain reaction (QMSP) after bisulfite conversion. Clinical and histological follow‐up according to a reference standard, defined in advance, were available for 198 of 210 patients.RESULTS:In the whole cohort, cytology, FISH, DNA‐image cytometry, and QMSP achieved sensitivities of 83.7%, 78%, 79%, and 49.6%, respectively (specificities of 69.8%, 98.2%, 98.2%, and 98.4%, respectively). Subsequent to cytologically equivocal diagnoses, FISH, DNA‐image cytometry, and QMSP definitely identified malignancy in 79%, 83%, and 49%, respectively. With QMSP, 4 of 22 cancer patients with cytologically negative diagnoses were correctly identified.CONCLUSIONS:Thus, adjuvant FISH or DNA‐image cytometry in cytologically equivocal diagnoses improves diagnostic accuracy at comparable rates. Adjuvant QMSP in cytologically negative cases with persistent suspicion of lung cancer would enhance sensitivity. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.

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Copy number gains on 5p15, 6p11-q11, 7p12, and 8q24 are rare in sputum cells of individuals at high risk of lung cancer

Cited by 17 publications

References 24 publications

Automated detection of genetic abnormalities combined with cytology in sputum is a sensitive predictor of lung cancer

Automated detection of genetic abnormalities combined with cytology in sputum is a sensitive predictor of lung cancer

Familial risk for lung cancer

Equivocal cytology in lung cancer diagnosis

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