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

Abstract

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.

DNA aneuploidy combined with radial EBUS in the diagnosis of peripheral lung lesions

“…The DNA histograms of corresponding patterns were are shown in Figure 1 , which was described in previous study. 19 Among the 30 patients with malignancy (Table 1 ), four patients (13.3%) were pathology positive and DNA‐ICM negative. Eight patients (26.6%) were DNA‐ICM positive while pathology negative.…”

“…(b) Patients who were lost to follow‐up without a clear diagnosis. (c) Patients with clinical manifestation of infection or with a large amount of purulent bronchial secretion under bronchoscope were excluded, as our previous study showed high false positive rate in such patients 19 …”

“…The bronchial washings, which were from the target bronchial segment by R‐EBUS, were successively centrifuged, stained and fixed, according to methods previously reported 19 . The DNA content was tested by Feulgen staining of the nuclei, proportionally indicated by the depth of coloration of the nuclei.…”

“…The bronchial washings, which were from the target bronchial segment by R‐EBUS, were successively centrifuged, stained and fixed, according to methods previously reported. 19 The DNA content was tested by Feulgen staining of the nuclei, proportionally indicated by the depth of coloration of the nuclei. The nuclei of Feulgen‐stained cells are automatically scanned by an optical automated 3D moving platform and the DNA index (DI) or DNA content (c) is calculated.…”

Hypoxia-Nitric Oxide Axis and the Associated Damage Molecular Pattern in Cutaneous Melanoma

“…Of the many signaling mechanisms of NO, it is appreciated that epigenetic regulation has gained ground in recent years. NO promotes an immunosuppressive microenvironment by modifying the redox state of cells, reprogramming cellular metabolism, and inducing changes in nucleic acids, lipids, and proteins [ 29 , 59 , 60 , 61 , 62 , 63 ]. All these effects of NO in melanoma are also supported by our results.…”