GSTM1, P53 and K-ras molecular detection in resectable non-small cell lung cancer by denaturing gradient gel electrophoresis-bronchoalveolar lavage fluid analysis.
BACKGROUND
Understanding molecular abnormalities could potentially lead to novel investigational approaches in the molecular epidemiology of lung cancer. These might include the identification of patients at high risk for primary NSCLC and the surveillance of patients with known NSCLC who are being treated using lung-sparing surgical strategies.


METHODS
The PCR-Denaturing Gradient Gel Electrophoresis (DGGE) strategy was used for primary tumors and corresponding bronchalveolare lavage (BAL) samples.


RESULTS
We recruited 36 consecutive patients with NSCLC, 28 (77.7%) males and 8 females (22.3%). DGGE showed a good rate of accuracy in the genetic screening of K-ras and p53 mutations in BAL specimens. Specific mutations were more often detected in BAL fluid from patients with not peripheral tumors than parenchymal or peripheral tumors (p53: 85.7%, p=0.0004; K-ras: 75%, p=0.001). p53 mutations were more frequent in BAL fluid from squamous cell carcinomas (22%) than from adenocarcinomas (15%). A significant correlation was observed between null GST-Ml genotype and p53 overall mutations (p=0.0003), K-ras mutations (p=0.02), non peripheral tumors (p=0.04) and smoking habits (p=0.002).


CONCLUSIONS
We observed that null GSTMl genotype is strongly related to p53 mutations. Individuals at high risk for primary NSCLC, such as heavy smokers or individuals exposed to occupational carcinogens, could be screened by BAL-analysis for cancer biomarkers of susceptibility like GSTM-1 in large scale molecular epidemiology studies.
Curigliano
G
G
European Institute of Oncology, Department of Medicine, Milano, Italy. giuseppe.curigliano@ieo.it
Ferretti
G
G
Mandalà
M
M
De Pas
T
T
Calabrò
M G
MG
Solli
P
P
Noberasc
C
C
de Braud
F
F
D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D004586:Electrophoresis / Q000379:methods; D005091:Exons; D005260:Female; D016158:Genes, p53; D011905:Genes, ras; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics*
D005982:Glutathione Transferase; D016159:Tumor Suppressor Protein p53; D018631:ras Proteins