Widespread molecular alterations present in stage I non-small cell lung carcinoma fail to predict tumor recurrence

Fabien K. Baksh, Sanja Dacic, Sydney D. Finkelstein, Patricia A. Swalsky, Siva Raja, Eizaburo Sasatomi, James D. Luketich, Hiran C. Fernando, Samuel A. Yousem

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)28-34
Number of pages7
JournalModern Pathology
Volume16
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Keywords

  • Loss of heterozygosity
  • Non-small cell lung carcinoma
  • Prognosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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