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

Katz, Ruth L.; Zaidi, Tanweer M.; Fernández, Ricardo; Zhang, Jingpin; He, Weixiang; Acosta, Charisse; Daniely, Michal; Madi, Lea; Vargas, Mary A; Dong, Qiong; Gao, Xiaoying; Jiang, Feng; Caraway, Nancy P.; Vaporciyan, Ara A.; Roth, Jack A.; Spitz, Margaret R.

doi:10.1038/modpathol.2008.71

Cited by 46 publications

(37 citation statements)

References 20 publications

(33 reference statements)

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“…23,24 Several attempts have been undertaken to use automated and semiautomated systems for the detection of cancer cells and dysplastic cells in sputum based on morphologic features of abnormal cell clusters, 25 ploidy measurements, [26][27][28][29][30] or the detection of genetic abnormalities with fluorescence in situ hybridization. 31 The majority of these studies reported very high sensitivities; however, we await the confirmation of the results from large-scale clinical trials. Recent technical developments have made it possible to combine flow cytometry with CT on the cellular level, allowing for cytometry in 3 dimensions.…”

Section: Discussionmentioning

confidence: 99%

Premalignant and malignant cells in sputum from lung cancer patients

Neumann

Meyer²,

Patten³

et al. 2009

Cancer Cytopathology

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BACKGROUND:The objective of this study was to assess the frequency of premalignant and malignant cells in sputum from patients with lung cancer and to measure the dependence of these cells on cancer stage, histologic type, tumor size, and tumor location.METHODS:This analysis included 444 patients with lung cancer. First, all patients were asked to produce sputum spontaneously; then, they underwent sputum induction. Slide preparations of the sputa were screened for the presence of abnormal cells.RESULTS:Of all patients with lung cancer who had produced adequate specimens, 74.6% had sputum that was positive for premalignant or worse cells, whereas 48.7% had sputum that was positive for malignant cells alone. Surprisingly, the presence of premalignant or worse cells in sputum depended only moderately on disease stage (82.9% of stage IV cancers vs 65.9% of stage I cancers), tumor size (78.6% of tumors >2 cm vs 64.7% of tumors ≤2 cm), and location (83.3% of central lesions vs 68% of peripheral lesions) and was found to be independent of histologic tumor type (78.4% of squamous cell carcinomas vs 71.5% of adenocarcinomas, 74.5% of small cell carcinomas, and 75% of large cell carcinomas).CONCLUSIONS:The findings of the current study suggested the important potential of sputum cytology for lung cancer detection and risk assessment across all stages, histologic types, tumor sizes, and locations. However, the high sensitivities in this study were achieved with a level of scrutiny not feasible in the laboratory routine. The diagnostic potential of sputum cytology may be exploited better through the standardization and automation of sputum preparation and analysis. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Premalignant and malignant cells in sputum from lung cancer patients

Neumann

Meyer²,

Patten³

et al. 2009

Cancer Cytopathology

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“…This study extends our previous research efforts to develop noninvasive or minimally invasive diagnostic means for lung cancer. 16,[20][21][22] Given the expenses associated with quantitative molecular analysis of multiple genes by a RT-qPCR platform, a marker panel with the smallest number of miRNAs and highest diagnostic accuracy would provide a cost-effective assay for squamous cell carcinoma of lung cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Sputum was collected from the participants as described in our recent reports. 16,[20][21][22] To further validate the identified sputum markers, we collected sputum specimens from an independent set of 67 lung squamous cell carcinoma patients and 55 healthy controls. The demographic and clinical characteristics of the cancer patients are summarized in Table 1.…”

Section: Patients and Clinical Specimensmentioning

confidence: 99%

Early detection of squamous cell lung cancer in sputum by a panel of microRNA markers

et al. 2010

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Squamous cell carcinoma is a common form of lung cancer, the leading cause of cancer deaths in the world. Identifying early stage lung squamous cell carcinoma patients who would benefit most from effective therapies will reduce the mortality. We have previously shown that microRNAs (miRNAs) were stably present in sputum and potentially useful in diagnosis of lung cancer. The objective of this study was to develop a panel of miRNAs that can be used as a sputum-based test for early stage squamous cell carcinoma of the lungs. This study contained three phases: (1) marker discovery by profiling miRNA expression signatures on 15 lung squamous cell carcinoma and matched normal lung tissue samples with GeneChip miRNA Array; (2) marker optimization by real-time quantitative RT-PCR on sputum of a case-control cohort of 48 stage I lung squamous cell carcinoma patients and 48 healthy individuals; and (3) marker validation on an independent set including 67 lung squamous cell carcinoma patients and 55 healthy subjects. On the surgical tissues, six miRNAs were identified, of which three were overexpressed and three were underexpressed in all 15 tumors. On the sputum samples of the case-control cohort, three (miR-205, miR-210 and miR-708) of the six miRNAs were selected, which in combination produced the best prediction in distinguishing lung squamous cell carcinoma patients from normal subjects with 73% sensitivity and 96% specificity. Validation of the marker panel in the independent populations confirmed the sensitivity and specificity that provided a significant improvement over any single one alone. The sputum markers showed the potential to improve the early detection of lung squamous cell carcinomas.

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“…Several studies indicate that abnormal sputum cells, in particular identifying genetic alterations associated with malignant transformation, may be useful in identifying individuals at high risk of lung cancer (24)(25)(26)(27)(28). 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).…”

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

Cited by 46 publications

References 20 publications

Premalignant and malignant cells in sputum from lung cancer patients

Premalignant and malignant cells in sputum from lung cancer patients

Early detection of squamous cell lung cancer in sputum by a panel of microRNA markers

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

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