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Detection of Loss of Heterozygosity by High-Resolution Fluorescent System in Non-small Cell Lung Cancer^*

Association of Loss of Heterozygosity With Smoking and Tumor Progression

^* From the Department of Surgery and Science (Drs. Yoshino, Fukuyama, Kameyama, Shikada, Maehara, and Sugimachi), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and the Pathological Research Laboratory (Dr. Oda), National Kyushu Cancer Center, Fukuoka, Japan.

Correspondence to: Ichiro Yoshino, MD, PhD, Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan; e-mail: iyoshino{at}surg2.med.kyushu-u.ac.jp

Background: We recently developed a novel system for detecting microsatellite alteration, which is an important process in carcinogenesis. In patients with non-small cell lung cancer (NSCLC), loss of heterozygosity (LOH) is frequently observed and causes functional disorders of tumor suppressor genes.

Patients and methods: In a consecutive series of 51 patients with NSCLC who had undergone a surgical resection, microsatellite instability (MSI) and LOH in tumors were analyzed by polymerase chain reaction using five fluorescence-labeled dinucleotide markers (D2S123, D5S107, D10S197, D11SS904, and D13S175) and an autosequencer.

Results: MSI was detected in only one patient (2.0%) with only one marker. LOH was detected in at least one chromosomal region that was tested in 39 patients (76%). The mean (± SD) number of LOHs detected by each marker was 1.74 ± 1.40, with 1 LOH detected in 10 patients, 2 LOHs detected in 15 patients, 10 LOHs detected in 3 patients, 1 LOH detected in 4 patients, and 3 LOHs detected in 5 patients. The number of LOHs detected in each patient was significantly associated with the pack-year index ( = 0.501; p = 0.0004), although there was no relationship with having a history of multiple cancers and familial cancer. Patients with stage IA disease showed a significantly lower number of LOHs than did patients with other stages of disease (1.15 vs 2.38, respectively; p = 0.0013).

Conclusion: LOH is very common in patients with NSCLC, and the number of LOHs increases with increases in smoking, suggesting the presence of an important event in lung carcinogenesis.

Key Words: loss of heterozygosity • microsatellite instability • microsatellite marker • non-small cell lung cancer • smoking habit

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