Widespread molecular alterations present in stage I non-small cell lung carcinoma fail to predict tumor recurrence.
Stage I non-small cell carcinoma (NSCLC) of the lung is typically treated with surgery alone, but with a 30 to 40% recurrence rate. Prognostic factors to stratify these patients into high- and low-risk groups would be of significant clinical value, but published data are conflicting. We studied 39 Stage I NSCLC treated with resection alone, followed for a minimum of 5 years, and divided into recurrent (RC) and non-recurrent (NRC) groups (n = 12 and 27, respectively). Allelic imbalance (loss of heterozygosity, LOH) involving genomic regions containing L-myc (1p32), hOGG1 (3p26), APC/MCC (5q21), c-fms (5q33.3), p53 (17p13), and DCC (18q21), and point mutational change in K-ras-2 (12p12) were studied by PCR-based microsatellite analysis and DNA sequencing. Mutations in k-ras-2 were seen in 25% and 19% of RC and NRC tumors, respectively, most frequently in adenocarcinomas. LOH in the RC and NRC respectively were 50% and 37% for L-myc, 60% and 33% for hOGG1, 60% and 50% for APC, 38% and 35% for c-fms, 78% and 75% for p53, and 17% and 45% for DCC. No statistical significance was seen comparing any of the allelic alterations with recurrence. LOH for hOGG1 and L-myc were more commonly seen in squamous cell carcinomas. Stage I NSCLC are genetically heterogeneous with respect to mutation acquisition. The approach of investigating a panel of genes for alterations can be applied to any given tumor type, and provides information on patterns of mutations/LOH that can help us better understand the molecular biology of tumorigenesis.
Baksh
Fabien K
FK
Department of Pathology, University of Pittsburgh Medical Center, Presbyterian University Hospital, Pittsburgh, Pennsylvania 15213, USA.
Dacic
Sanja
S
Finkelstein
Sydney D
SD
Swalsky
Patricia A
PA
Raja
Siva
S
Sasatomi
Eizaburo
E
Luketich
James D
JD
Fernando
Hiran C
HC
Yousem
Samuel A
SA
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D011905:Genes, ras; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis
D004273:DNA, Neoplasm