Widespread Molecular Alterations Present in Stage I Non-Small Cell Lung Carcinoma Fail to Predict Tumor Recurrence

• Published in: Modern pathology Vol. 16; no. 1; pp. 28 - 34
• Main Authors: Baksh, Fabien K, Dacic, Sanja, Finkelstein, Sydney D, Swalsky, Patricia A, Raja, Siva, Sasatomi, Eizaburo, Luketich, James D, Fernando, Hiran C, Yousem, Samuel A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2003; Elsevier Limited
• Subjects: Aged; Cancer; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - surgery; DNA, Neoplasm - analysis; Female; Genes, ras; Humans; Loss of Heterozygosity; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Male; Medical prognosis; Middle Aged; Mutation; Neoplasm Recurrence, Local; Neoplasm Staging; Non-small cell lung carcinoma; Pathology; Patients; Polymerase Chain Reaction; Predictive Value of Tests; Prognosis; Tumors; United States > US; Pittsburgh Pennsylvania; Non-small cell lung carcinoma; Prognosis; Loss of heterozygosity
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1097/01.MP.0000044621.08865.C4

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.