Multicolor Fluorescence In Situ Hybridization For The Detection Of Lung Cancer In Bronchoscopic Brushing Specimens

BACKGROUND & OBJECTIVE: Conventional cytology plays an important role in the diagnosis of lung cancer. especially in the examination of sputum, bronchial brushing specimens and pleural effusions. Cytologic diagnoses are made by experienced cytologists who can properly evaluate the morphologic features of malignant cells. However, this judgment is sometimes difficult when the morphologic changes associated with malignancy are mild. Aneuploidy is the most common feature of many solid tumors, including lung cancer. This study aimed to reveal the aberrations of some chromosomes in lung cancer, and to compare the relative sensitivity and specificity of cytology and multicolor fluorescence in situ hybridization (M-FISH) for the detection of lung cancer in bronchoscopically obtained brushing specimens.METHODS: Eight-two randomly selected bronchial brushing specimens (71 tumors, 11 benign lesions) and seventeen lung cancer and pathology-negative incisal margin tissues were double-blindly examined by interphase M-FISH with DNA probes specific for chromosomes 3, 6, 7, 8, 11, 12 and 17 which are reported to be frequently gained in lung cancer. Based on the data of tumor adjacent tissues, aneuploidy criteria was defined as FISH signal loss in >20% nuclei or FISH signal gain in >20% nuclei. The specificity of each chromosome enumeration probe (CEP) was detected by metaphase chromosomes of lymphocytes in normal peripheral blood. The relationship between chromosome aberrations and clinicopathologic parameters was analyzed; a comparison of cytology and M-FISH for the detection of lung cancer in bronchoscopic brushing specimens was performed.RESULTS: High positive-aneuploidy rate of chromosomes 3,.6, 7, 8, 11, 12 and 17 was detected in both bronchial brushing specimens and lung cancer tissues. The copy number gains of these chromosomes mentionen above were 76.0% (38/50), 48.1 % (26/54), 61.8% (42/68), 45.0% (27/60). 44.1% (30/68), 45.9% (28/61) and 41.2 % (28/68) in 71 bronchial brushing specimens from patients with lung cancers and 92.9% (13/14), 100.0% (11/11), 88.2% (15/17), 76.5% (13/17), 75.0% (12/16), 87.5% (14/16), 94.1% (16/17) in 17 lung cancer tissues, respectively. The anueploidy of chromosome 12 and 17 were significantly correlated with advanced clinicopathologic stage (P < 0.05), no other statistically significant relation was found between chromosome aberrations and clinicopathologic parameters. Moreover, M-FISH (containing four probes of chromoses 3, 6, 7, 12, and 17) was more sensitive than cytology (61.1～71.2% vs 55.4～55.9%) for detecting malignancy in brushing samples, and the combination of M-FISH and cytology significantly araised the sensitivity to 87.3～92.2% over cytology alone (P < 0.01).CONCLUSION: High aneuploidy frequency of chromosomes 3, 6, 7, 8, 11, 12 and 17 was detected in both bronchial brushing specimens and lung cancer tissues. The rate of chromosomes 12 and 17 aberration was probably a prognostic factor of patients with lung cancer. M-FISH (containing four probes of chromosomes 3, 6, 7, 12, and 17) can detect lung cancer cells with anueploidy in bronchial brushing specimens. The sensitivity was superior to that of routine cytology. M-FISH in conjuction with routine cytology will contribute to the improvement of the diagnosis for lung cancer.