DNA-Based Sputum Cell Image Analysis for Lung Cancer in a Clinical Setting

Terčelj, Marjeta; Aleš, Andreja; Rott, T; Sever, Nejc; Prodnik, Luka; Eržen, Janez; Primic-Žakelj, Maja; Rylander, Ragnar

doi:10.1159/000325602

Cited by 3 publications

(8 citation statements)

References 27 publications

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“…For instance, the genetic/epigenetic changes discussed above clearly lack adequate diagnostic abilities. The DNA-based buccal image analysis had a sensitivity and specificity of 61 %, which is clearly inadequate for population screening (16). However, the potential of field carcinogenesis as a diagnostic tool for lung cancer screening was highlighted by a seminal report that with an 80-gene microarray signature from the “normal” right main-stem bronchial epithelium, one could achieve an 80% sensitivity, 84% specificity for discriminating smokers with and without lung cancer (17).…”

Section: Discussionmentioning

confidence: 99%

Optical Detection of Buccal Epithelial Nanoarchitectural Alterations in Patients Harboring Lung Cancer: Implications for Screening

et al. 2010

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We have recently developed a novel optical technology, partial wave spectroscopic (PWS) microscopy, which is exquisitely sensitive to the nanoarchitectural manifestation of the genetic/epigenetic alterations of field carcinogenesis. Our approach was to screen for lung cancer by assessing the cheek cells based on emerging genetic/epigenetic data which suggests that the buccal epithelium is altered in lung field carcinogenesis. We performed PWS analysis from microscopically normal buccal epithelial brushings from smokers with and without lung cancer (n = 135). The PWS parameter, disorder strength of cell nanoarchitecture (Ld), was markedly (>50%) elevated in patients harboring lung cancer compared with neoplasia-free smokers. The performance characteristic was excellent with an area under the receiver operator characteristic curve of >0.80 and was equivalent for both disease stage (early versus late) and histologies (small cell versus non–small cell lung cancers). An independent data set validated the findings with only a minimal degradation of performance characteristics. Our results offer proof of concept that buccal PWS may potentially herald a minimally intrusive prescreening test that could be integral to the success of lung cancer population screening programs.

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Section: Discussionmentioning

confidence: 99%

Optical Detection of Buccal Epithelial Nanoarchitectural Alterations in Patients Harboring Lung Cancer: Implications for Screening

et al. 2010

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“…Several studies have reported that SDIC and automated SDIC improve sensitivity of detection of lung cancer over conventional pathology-based cytology and suggest that SDIC might be useful for early detection of lung cancer (24,(29)(30)(31)(32)(33)(34)(35). The extent to which SDIC data can improve lung cancer risk prediction is unclear.…”

Section: Introductionmentioning

confidence: 99%

Incremental Value of Pulmonary Function and Sputum DNA Image Cytometry in Lung Cancer Risk Prediction

Tammemägi

Lam²,

McWilliams³

et al. 2011

Cancer Prevention Research

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Lung cancer is the leading cause of cancer death worldwide. Accurate prediction of lung cancer risk is of value for individuals, clinicians, and researchers. The aims of this study were to characterize the associations between pulmonary function and sputum DNA image cytometry (SDIC) and lung cancer, and their contributions to risk prediction. During 1990 to 2007, 2,596 high-risk individuals were enrolled and followed prospectively for development of lung cancer (n ¼ 139; median follow-up 7.7 years) in trials at the British Columbia Cancer Agency. At baseline, an epidemiologic questionnaire was administered, sputum was collected for aneuploidy measurement and spirometry was obtained. Multivariable logistic models were prepared including known lung cancer predictors (model 1), that additionally included percent-expected-forced expiratory volume in 1 second [forced expiratory volume in 1 second (FEV 1 %), model 2], and that additionally included SDIC (model 3). Prediction was assessed by evaluating discrimination (receiver operator characteristic area under the curve (ROC AUC)) and calibration. Net reclassification indices (NRI) were calculated with cutoff points for 8-year risks identifying low, intermediate, and high risk at 1.5% and 3%. Lung cancer risk increased with decline in FEV 1 %, but did so more for men than for women (interaction P < 0.001). SDIC demonstrated a dose-response with lung cancer (P ¼ 0.022). The ROC AUCs for models 1, 2, and 3 were 0.718 (95% CI: 0.671-0.765), 0.767 (95% CI: 0.725-0.809), and 0.773 (95% CI: 0.732-0.815), respectively. Model 2 versus 1 had a NRI of 12.6% (P < 0.0001) and model 3 versus 2 had a NRI of 3.1% (P ¼ 0.059). Spirometry and SDIC data substantially and minimally improved lung cancer prediction, respectively. Cancer Prev Res; 4(4); 552-61. Ó2011 AACR.

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“…It is reported that the cells with DNA content of more than 5c could possibly be found in some benign lung disease. 14 , 15 One of mechanisms could be cellular damage induced by oxygen radicals or inflammation, which is a common reaction preceding or present in a variety of diseases. In our study, 8.7% (26/300) patients with benign lung diseases had false positive results of DNA‐ICM.…”

Section: Discussionmentioning

confidence: 99%

“… 16 , 17 , 18 But in a clinical setting mixed with a variety of nonmalignant pulmonary diseases, the specificity of DNA‐ICM for diagnosing lung cancer is obviously decreased. 14 …”

Section: Introductionmentioning

confidence: 99%

“…When sputum DNA‐ICM was applied to detect lung cancer in high‐risk patients and controls, a high specificity and an increased sensitivity compared to conventional cytology were reported 16–18 . But in a clinical setting mixed with a variety of nonmalignant pulmonary diseases, the specificity of DNA‐ICM for diagnosing lung cancer is obviously decreased 14 …”

Section: Introductionmentioning

confidence: 99%

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DNA image cytometric analysis of bronchial washings as an adjunct for the detection of lung cancer in a clinical setting

Guo

et al. 2022

Cancer Medicine

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Background DNA aneuploidy has a potential to become an adjunct to conventional cytology for diagnosis of lung cancer, but its value in bronchial washings has not been well evaluated. Methods We conducted a retrospective study on patients who underwent bronchoscopy and the bronchial washings were submitted for both cytology and DNA image cytometry (DNA‐ICM) examination. The sensitivity and specificity of two methods and both in combination were compared. Analysis of clinical subgroups and DNA histogram were also performed. Results The study included 626 patients (326 patients with lung cancer and 300 patients with benign lung diseases). The sensitivity of cytology, DNA‐ICM, and combination test for lung cancer were 53.3%, 62.3%, and 75.8%, respectively, and the sensitivity of DNA‐ICM and combination test were superior to that of cytology ( p < 0.05). A modest reduction of specificity was found in DNA‐ICM compared with cytology (91.3% vs. 98.3%, p < 0.05). Subgroup analysis showed there was no significant difference in sensitivity of DNA‐ICM between the visible tumor group and the invisible tumor group (66.5% vs. 56.9%, χ 2 = 3.114, p = 0.078). Among 101 patients with invisible endobronchial tumor, the positive rates for DNA‐ICM of washing, cytology of washing, brushing and biopsy were 62.4%, 41.6%, 40.6%, and 45.5%, respectively. DNA‐ICM in combination with the basic bronchoscopy techniques could increase the sensitivity from 67.3% to 87.1% ( p = 0.000). The DNA histogram analysis showed 25.3% washing samples of lung cancer were diploid pattern, 49.4% were scattered aneuploid cells pattern, and 25.3% were aneuploid peaks pattern. Small cell lung cancer had the highest proportion of aneuploid peaks pattern ( p < 0.05). Conclusions DNA‐ICM could be used as an adjunct for the detection of lung cancer. The combination of DNA‐ICM and basic bronchoscopy techniques could significantly increase the sensitivity, especially for the patients suspected of peripheral lung cancer, and contribute to select subjects for advanced bronchoscopy.

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DNA-Based Sputum Cell Image Analysis for Lung Cancer in a Clinical Setting

Cited by 3 publications

References 27 publications

Optical Detection of Buccal Epithelial Nanoarchitectural Alterations in Patients Harboring Lung Cancer: Implications for Screening

Optical Detection of Buccal Epithelial Nanoarchitectural Alterations in Patients Harboring Lung Cancer: Implications for Screening

Incremental Value of Pulmonary Function and Sputum DNA Image Cytometry in Lung Cancer Risk Prediction

DNA image cytometric analysis of bronchial washings as an adjunct for the detection of lung cancer in a clinical setting

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