| Title | Promoter hypermethylation for molecular nodal staging in non-small cell lung cancer. | | Author(s) | Safar AM, Spencer H, Su X, Cooney CA, Shwaiki A, Fan CY | | Institution | Department of Medicine, The University of Arkansas for Medical Sciences, Little Rock, AR, USA. SafarAhmedM@uams.edu | | Source | Arch Pathol Lab Med 2007 Jun; 131(6):936-41. | | MeSH | Adult
Aged
Aged, 80 and over
Carcinoma, Non-Small-Cell Lung
DNA Methylation
DNA, Neoplasm
Female
Humans
Lung Neoplasms
Lymph Nodes
Male
Middle Aged
Neoplasm Staging
Polymerase Chain Reaction
Prognosis
Promoter Regions (Genetics)
Retrospective Studies
Survival Rate
| | Abstract | CONTEXT: Even among cases of non-small cell lung cancer (NSCLC) in the most favorable stage (IA), the disease-specific mortality is 25% or greater. One plausible explanation implicates the simplistic standard pathologic procedures used to designate lymph node involvement. A more sensitive assessment of the nodal status may improve staging.
OBJECTIVE: To determine the prognostic impact of detecting an abnormal molecular event (promoter hypermethylation in a set of relevant genes) in histologically uninvolved lymph nodes in resected NSCLC.
DESIGN: In this retrospective analysis of archived material, we examined DNA extracted from lymph nodes of stage I NSCLC (n = 180). Patients underwent surgery between 1991 and 1995 in a single institution. Methylation-specific polymerase chain reaction was used to detect promoter hypermethylation in a panel of 8 genes. Survival data were extracted from the computerized database at the Tumor Registry.
RESULTS: Evidence of promoter hypermethylation in at least 1 gene was detected in 67% of these N0 nodes. The most commonly hypermethylated gene was E-cadherin (53%). The hypermethylation frequency for the remaining genes were as follows: APC, 5%; p16, 9%; MGMT, 11%; hMLH1, 15%; RASSF1A, 4%; DAP kinase, 9%; and ATM, 19%. The presence of promoter hypermethylation in 2 or more genes did not influence the overall, median, or 5-year survival rates.
CONCLUSIONS: Identifying promoter hypermethylation (in our panel) in N0 lymph nodes in stage I NSCLC cannot be recommended for clinical decision making. Molecular abnormalities, including those found in cancer by qualitative methylation-specific polymerase chain reaction, are not synonymous with established, histologically detectable metastasis. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 17550322 |
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