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We detected tumor-associated aberrant hypermethylation of the p16 gene in plasma DNA from 105 non-small cell lung cancer (NSCLC) patients (65 squamous cell carcinoma (SCC) and 40 adenocarcinoma (ADC)) and 92 matched tumor DNA samples, using a modified semi-nested methylation-specific PCR (MSP). This technique increased the sensibility of detecting p16 hypermethylation from DNA samples in varying stages. p16 hypermethylation was present in 73.3% (77/105) of the plasma samples, and 79.3% (73/92) of the tumor samples. Among those cases with methylated p16 sequence in tumor samples, 87.7% (64/73) also demonstrated this epigenetic alteration in the corresponding plasma DNA. Only patients whose tumor cells had hypermethylated p16 gene exhibited aberrant methylation in their plasma samples. Regarding different clinical stages of SCC and ADC, the frequencies of p16 hypermethylation in plasma DNA were nearly the same as those in corresponding tumors, except for stage I ADC. Our study indicated that aberrant methylation of p16 may be an excellent biomarker for early diagnosis and follow-up of NSCLC patients, and MSP is a reliable method for these purposes. [Copyright &y& Elsevier]

In the present study, we used 22 microsatellite markers flanking to or within 13 known or candidate tumor suppressor genes (TSGs) to detect loss of heterozygosity (LOH) in these chromosomal regions among 41 cases of non-small cell lung cancer, including 28 squamous cell carcinoma (SCC) and 13 adenocarcinoma (ADC). The studied TSGs comprised FHIT, VHL, APC, PRLTS, p16, IFNA, PTEN, p57, ATM, p53, BRCA1, DPC4 and DCC. Our data demonstrated frequent allelic losses of FHIT, p53, IFNA, VHL and p16 in both SCC and ADC. PTEN and ATM showed the least frequency of LOH, while no deletion of BRCA1 was detected in all tumor samples. LOH analysis of PRLTS was extended to 26 cases of ADC, which demonstrated significantly higher frequency of LOH than SCC. Our data indicated a possible correlation between specific TSG(s) and either histological type of lung cancer, and more attention should be paid to the PRLTS gene, which might play an important role in the development of ADC. [Copyright &y& Elsevier]