K-ras genotypes and prognosis in non-small-cell lung cancer

Background: Despite major advances in the treatment of many kinds of cancer over the past 25 years, the overall 5-year survival of non-small-cell lung cancer patients has scarcely improved. Even in stage I which has the best outcome long-term survival still falls below 70%. Since intriguing data sug...

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Published inAnnals of oncology Vol. 6; no. suppl-3; pp. S15 - S20
Main Authors Rosell, R., Monzo, M., Molina, F., Martinez, E., Pifarre, A., Moreno, I., Mate, J. L., Anta, J. M. de, Sanchez, M., Font, A.
Format Journal Article Conference Proceeding
LanguageEnglish
Published Oxford Oxford University Press 1995
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Summary:Background: Despite major advances in the treatment of many kinds of cancer over the past 25 years, the overall 5-year survival of non-small-cell lung cancer patients has scarcely improved. Even in stage I which has the best outcome long-term survival still falls below 70%. Since intriguing data suggest that the identification of genetic markers might allow prognosis to be assessed case by case. We were prompted to evaluate K-ras gene mutations as a putative prognostic marker in this neoplasm. Materials and methods: We used the polymerase chain reaction (PCR) followed by allele specific oligonucleotide (ASO) hybridization or single-strand conformation polymorphism (SSCP) assays, to detect K-ras mutations in DNA from formalin-fixed, paraffin-embedded tumor samples. K-ras mutations were examined in 192 stage I to IV non-small-cell lung cancer patients. Results: K-ras mutations were detected in 51 of 192 of the cases studied (27%). All K-ras mutations detected by PCR/ASO hybridization were also identified by SSCP. In stage I disease, the median survival time was 46 months in those patients whose tumors had no K-ras mutations and 21 months in those with aspartic acid and serine mutations at K-ras codon 12; in patients with stage IIIA disease, median survival time was 16 months in the K-ras negative group and 7 months in the aspartic acid and serine mutation group. No significant differences were observed for the remaining amino acid substitutions of K-ras, nor were they observed at all in more advanced disease. Conclusion: K-ras gene status has strong prognostic value in patients with stage IIIA non-small-cell lung cancer. The survival curve for patients with stage I and K-ras codon 12 aspartic or serine mutations is close to that of patients with stage IIIA without K-ras mutations. However, a non-small-cell lung cancer K-ras genotypic classification should be validated in larger studies.
Bibliography:Correspondence to: Rafael Rosell, M.D. University Hospital Germans Trias i Pujol Medical Oncology Service Box 72 08916 Badalona, Barcelona Spain
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ISSN:0923-7534
1569-8041
DOI:10.1093/annonc/6.suppl_3.S15