Tuberc Respir Dis.  2006 Feb;60(2):160-170.

p16(INK4a) Promoter Hypermethylation in Sputum, Blood, and Tissue from Non-Small Cell Lung Cancer and Pulmonary Inflammation

• Kim JP
• Kim KM
• Kwon SS
• Kim YK
• Kim KH
• Moon HS
• Song JS
• Park SH
• Ahn JH

Abstract

BACKGROUND: The aberrant promoter hypermethylation of p16(INK4a), as a tumor suppressor gene, is contributory factor to non-small cell lung cancer(NSCLC). However, its potential diagnostic impact of lung cancer is unclear. This study measured the level of p16(INK4a) promoter hypermethylation in the sputum and blood, and compared this with the level measured in the tissue obtained from NSCLC and pulmonary inflammation.
METHODS
Of the patients who visited the Our Lady of Mercy Hospital in Incheon, Korea for an evaluation of a lung mass and underwent blood, sputum, and tissue tests, 23patients (18 NSCLC, 5 pulmonary inflammation) were enrolled in this study. DNA was extracted from each sample and the level of p16(INK4a) methylation was determined using methylation-specific polymerase chain reaction.
RESULTS
p16(INK4a) methylation of the blood was observed in 88.9% (16 of 18) and 20.0% (1 of 5) of NSCLC and from pulmonary inflammation samples, respectively (P=0.008). Methylation of the sputum was observed in 83.3% (10 of 12) 80.0% (4 of 5) of NSCLC and pulmonary inflammation samples, respectively (P=1.00). Among the 8 NSCLC tissue samples, methylation changes were detected in 75.0% of samples (6 cases). Four out of seven tissue samples (57.1%) showed concordance, being methylated in both the blood and sputum.
CONCLUSIONS
There was a higher level of p16(INK4a) methylation of the blood from NSCLC patients than from pulmonary inflammation. The tissue showed a high concordance with the blood in the NSCLC samples. These findings suggest that p16(INK4a) promoter hypermethylation of the blood can used to discriminate between NSCLC and pulmonary inflammation.

Keyword

p16(INK4a) promoter hypermethylation; Non-small cell lung cancer; Pulmonary inflammation

MeSH Terms

Carcinoma, Non-Small-Cell Lung*
Cyclin-Dependent Kinase Inhibitor p16*
DNA
Genes, Tumor Suppressor
Humans
Incheon
Korea
Lung
Lung Neoplasms
Methylation
Pneumonia*
Polymerase Chain Reaction
Sputum*
Cyclin-Dependent Kinase Inhibitor p16
DNA

Figure

• 

  Figure 1. Analysis of p16INK4a promoter hypermethylation in blood from NSCLC and pulmonary inflammation. Bisulfite modified DNA was amplified by primers specific to unmethylated or methylated alleles of p16INK4a. The prescence of visible PCR product in each lanes marked unmethylated or methylated.

• 

  Figure 2. Analysis of p16INK4a promoter hypermethylation in sputum from NSCLC and pulmonary inflammation.

• 

  Figure 3. Analysis of p16INK4a promoter hypermethylation in tissue from NSCLC. Methylation was observed in six of eight cases.

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