Pulmonary Cytology with FISH for the Detection of Lung Cancer on Bronchial Brushing
Detection of lung cancer in bronchial brushing specimens collected during bronchoscopy
This test is most useful when used on specimens from peripheral lung lesions, especially those <2 cm in size
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The National Cancer Institute estimates that more than 219,000 men and women in the United States will be diagnosed with cancer of the lung and bronchus in 2009. The dismal 5-year survival of 15% for all patients diagnosed with lung cancer has been attributed to the fact that more than 80% have advanced disease at the time of diagnosis. Cytologic analysis of brushing specimens collected during bronchoscopy is widely used to help diagnose malignancy in patients suspected of having lung cancer. Previous studies have shown that in centrally located tumors, the diagnostic sensitivity of bronchial brushing cytology ranges from 23% to 93% (mean 61%).(1) However, the sensitivity is considerably lower in peripheral tumors ranging from 15% to 84% (mean 54%), and even lower in those patients with nodules <2 cm in size (5%-76%; mean 34%).(1) These data illustrate the need for improved clinical or laboratory tests to accurately detect early stage disease, especially in small, peripherally located tumors.
FISH is a technique that utilized fluorescently labeled DNA probes to examine cells for chromosomal alterations. FISH can be used to detect cells with chromosomal changes (eg, aneusomy) that are indicative of malignancy. The FISH for lung cancer assay utilizes a multicolor, multitarget probe mixture (Abbott Molecular, Inc.), which contains locus-specific probes to 5p15 (TERT), 7p12 (EGFR), 8q24 (c-Myc), and a centromeric probe to chromosome 6, to detect malignant cells in bronchoscopically obtained brushing specimens. Studies in our laboratory and other laboratories indicate that the sensitivity of FISH for the detection of lung cancer is superior to that of conventional cytology.(2-3)
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
An interpretive report is provided, based on the combination of routine cytology and FISH results.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
An abnormal FISH result does not indicate the histologic subtype, stage, grade, or location of the tumor.
A study of 312 patients with bronchoscopically obtained bronchial brushings from central and peripheral lung lesions compared the relative sensitivities and specificities of cytology alone and cytology with FISH for detecting primary lung carcinoma.(2) Bronchoscopic biopsy, surgical resection, needle aspirate results and/or clinical indication of lung cancer was used as the gold standard. Any mucosal abnormalities visualized during the bronchoscopic procedure were brushed and designated as central lesions. Peripheral lesions were defined as lesions beyond the segmental bronchi that required fluoroscopic guidance for visualization.
For peripheral lung lesions, the sensitivity of cytology with FISH for lung cancer (n=110) was significantly higher than cytology alone for peripheral lesions <2 cm (46% vs. 4%; P <0.001) and >2 cm (61% vs. 31%; P <0.001). There was no significant difference in specificity between cytology with FISH and cytology alone in lesions <2 cm
(87% vs. 100%; P=0.062) and >2 cm (98% vs. 100%; P=1.00) among patients without evidence of cancer (n=109).
For central lung lesions, sensitivity of cytology alone and cytology with FISH was 48% (23/48) and 81% (39/48) (P <0.001), respectively. However, there was a significant difference observed in the specificity of cytology alone and cytology with FISH (100% vs. 78%; P <0.001) among patients without evidence of cancer (n=45).
Lung cancer detection of cytology with FISH and cytology alone were compared for patients with non-small cell carcinoma at early (stages IIb and lower; n=38) and advanced (stage IIIa and higher; n=77) stage disease. The sensitivity of cytology with FISH was significantly higher than cytology alone for early (58% vs. 32%; P=0.002) and advanced (65% vs. 36%; P <0.001) stage disease.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Rivera MP, Mehta AC; Initial diagnosis of lung cancer: Accp evidence-based clinical practice guidelines (2nd edition). Chest 2007;132:131S-148S
2. Voss JS, Kipp BR, Halling KC, et al: Fluorescence in situ Hybridization Reflex Algorithm Improves Lung Cancer Detection in Bronchial Brushing Specimens. (Unpublished data/under review)
3. Halling KC, Rickman OB, Kipp BR, et al: A comparison of cytology and fluorescence in situ hybridization for the detection of lung cancer in bronchoscopic specimens. Chest 2006;130:694-701
4. Jett JR, Midthun DE: Screening for lung cancer: current status and future directions: Thomas A. Neff lecture. Chest 2004 May:125:158S-162S
5. Mazzone P, Jain P, Arroliga AC, et al: Bronchoscopy and needle biopsy techniques for diagnosis and staging of lung cancer. Clin Chest Med 2002:23:137-158