Computerized analysis of cytology and fluorescence in situ hybridization (FISH) in induced sputum for lung cancer detection

Guber, Alexander; Greif, Joel; Rona, Roni; Fireman, Elizabeth; Madi, Lea; Kaplan, Tal; Yemini, Zipi; Gottfried, Maya; Katz, Ruth L.; Daniely, Michal

doi:10.1002/cncy.20094

Cited by 11 publications

(12 citation statements)

References 21 publications

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“…6–8,12–19 Table 1 summarizes eleven of these studies according to design, assay platform, conclusions, and criteria for positivity. Most of these investigations used sputum specimens from patients diagnosed with lung cancer and convenience samples of high risk individuals, e.g.…”

Section: Introductionmentioning

confidence: 99%

Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer

Barón

Kako

Feser

et al. 2017

Journal of Thoracic Oncology

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Introduction Low dose CT screening for lung cancer has a high false positive rate with frequent discovery of indeterminate pulmonary nodules. Noninvasive biomarkers are needed to reduce false positives and improve risk stratification. A retrospective longitudinal evaluation was performed to assess chromosomal aneusomy in sputum via fluorescence in situ hybridization (CA-FISH) in four nested case-control studies. Methods ROC analysis resulted in two grouped cohorts: High Risk (CO High Risk and CO Nodule; 68 Cases, 69 controls) and Screening (ACRIN/NLST and PLuSS; 97 Cases, 185 controls). The CA-FISH assay was a 4-target DNA panel encompassing EGFR and MYC genes, and the 5p15 and centromere 6 regions or the FGFR1 and PIK3CA genes. A 4-category scale: normal, probably normal, probably abnormal and abnormal was applied. Sensitivity, specificity, and positive and negative likelihood ratios (LR+, LR−) (with 95% CI) were estimated for each cohort. Results Sensitivity and specificity were, respectively, 0.67 (0.55, 0.78) and 0.94 (0.85, 0.98) for High Risk subjects and 0.20 (0.13, 0.30) and 0.84 (0.78, 0.89) for Screening subjects. LR+ and LR− were, respectively, 11.66 (4.44, 30.63) and 0.34 (0.24, 0.48) for High Risk; and 1.36 (0.81, 2.28) and 0.93 (0.83, 1.05) for Screening subjects. Conclusion The high positive likelihood ratio of sputum CA-FISH indicates it could be a useful adjunct to LDCT for lung cancer in high risk settings. For screening, however, its low positive likelihood ratio limits clinical utility. Prospective assessment of CA-FISH in the incidentally-identified indeterminate nodule setting is ongoing in the Colorado Pulmonary Nodule Biomarker Trial.

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Section: Introductionmentioning

confidence: 99%

Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer

Barón

Kako

Feser

et al. 2017

Journal of Thoracic Oncology

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“…CT screening of high-risk patients vs. symptomatic patients, central vs. peripheral tumors, brush cytology vs. fine-needle aspiration). Using a similar approach, Guber et al [13] recently described a system for computer-assisted automated dual scanning of both morphological staining and matched FISH images for interactive review. This also allows targeting of morphologically abnormal cells for quantitative FISH analysis [13].…”

Section: Diagnostic Multitarget Fishmentioning

confidence: 99%

“…Using a similar approach, Guber et al [13] recently described a system for computer-assisted automated dual scanning of both morphological staining and matched FISH images for interactive review. This also allows targeting of morphologically abnormal cells for quantitative FISH analysis [13]. Using dual FISH to detect deletions of 3p22.1 and 10q22.3 in sputum specimens, they achieved a high sensitivity of 92%.…”

Section: Diagnostic Multitarget Fishmentioning

confidence: 99%

Role of Fluorescence in situ Hybridization in Lung Cancer Cytology

Savic

Bubendorf²

2012

Acta Cytologica

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There are several challenges in lung cytology including equivocal cytological findings, lung cancer subclassification, and predictive marker analysis. Fluorescence in situ hybridization (FISH) detects chromosomal alterations that underlie the development and progression of cancer, and pinpoints targets of new anticancer drugs. Detection of such targets by FISH can be of diagnostic utility in morphologically difficult cases. Multitarget FISH with four different chromosomal probes improves the sensitivity of cytology in the diagnosis of lung cancer and clarifies equivocal cytological findings. FISH is becoming increasingly important in the field of predictive marker analysis. FISH is the gold standard to identify ALK rearrangements for treatment with the ALK inhibitor crizotinib (Xalkori). EGFR mutation analysis is the method of choice for selecting patients for therapy with EGFR tyrosine kinase inhibitors (TKIs), whereas the EGFR gene copy number has not been confirmed as a reliable predictive marker. MET amplification is an important mechanism of secondary resistance to EGFR TKIs and a candidate predictive marker for targeted second-line treatment of TKI-resistant non-squamous non-small cell lung cancer. FGFR1 amplification is a promising new marker in squamous cell carcinoma that may predict the response to FGFR1 inhibitors. In conclusion, there are an increasing number of clinically relevant FISH applications in lung cytology. We provide an overview on the current role of FISH in respiratory cytology.

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“…This method has been tested successfully by us and by other authors. 29,30 Chromosome 8, chromosome 17, and MYC were chosen for the current analysis based on the literature and our previous studies. [20][21][22][23]25,31 Chromosome 8 is the site of several genes that have crucial functions in the tumorigenesis of several solid and hematopoietic malignancies.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive detection of aneuploid cells in laryngeal epithelial precursor lesions

Shani

Primov-Fever

Wolf

et al. 2011

Cancer Cytopathology

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BACKGROUND:Most cases of laryngeal cancer are preceded by precursor lesions which, if left untreated, can progress toward an invasive cancer. The objective of this study was to investigate the presence of chromosomal numerical aberrations in cells that were collected by noninvasive brush sampling from laryngeal lesions.METHODS:Laryngeal brush samples from 52 patients were analyzed simultaneously for morphology and fluorescence in situ hybridization (FISH) using centromeric probes for chromosome 17, chromosome 8, and a locus‐specific instability (LSI) v‐myc avian myelocytomatosis viral oncogene homolog (myc) proto‐oncogene protein (C‐MYC) probe for the MYC gene. The patients were divided according to histopathologic diagnosis. Group 1 included patients with squamous cell carcinoma, carcinoma in situ, and severe dysplasia; Group 2 included patients with moderate dysplasia, mild dysplasia, and hyperplasia; and Group 3 included patients with benign nondysplastic lesions.RESULTS:The proportion of cells with MYC and chromosome 8 gains demonstrated significant trends toward being the highest in Group 1 and the lowest in Group 3 (P = .001 and P = .003, respectively). No significant trend was observed for chromosome 17. Mann‐Whitney Bonferroni‐corrected analyses revealed that the most significant contribution was the difference between Groups 1 and 3 (P = .0195 for MYC gains and P = .036 for chromosome 8 gains). When using a cutoff point of 4% aneuploid cells (ACs), both MYC and chromosome 8 differed significantly between groups (P = .030 and P = .037, respectively).CONCLUSIONS:The current results suggested that FISH analysis of brush samples obtained noninvasively from suspicious laryngeal lesions can augment the clinical examination in predicting the nature of the lesions and can aid clinicians in monitoring and follow‐up of high‐risk patients. Cancer (Cancer Cytopathol) 2011. © 2011 American Cancer Society.

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Computerized analysis of cytology and fluorescence in situ hybridization (FISH) in induced sputum for lung cancer detection

Abstract: BACKGROUND:Lung cancer results from a multistep process, whereby genetic and epigenetic alterations lead to a malignant phenotype. Somatic mutations, deletions, and amplifications can be detected in the tumor itself,

Cited by 11 publications

References 21 publications

Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer

Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer

Role of Fluorescence in situ Hybridization in Lung Cancer Cytology

Noninvasive detection of aneuploid cells in laryngeal epithelial precursor lesions

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