Prognostic significance of K-ras codon 12 mutations in patients with resected stage I and II non-small-cell lung cancer.
ABSTRACT The aim of this study was to investigate the prognostic importance of codon 12 K-ras mutations in patients with early-stage non-small-cell lung cancer (NSCLC).
We identified 260 patients with surgically resected stage I (n = 193) and stage II (n = 67) NSCLC with at least a 5-year follow-up. We performed polymerase chain reaction analysis of DNA obtained from paraffin-embedded NSCLC tissue, using mutation-specific probes for codon 12 K-ras.
K-ras mutations were detected in 35 of 213 assessable specimens (16.4%). K-ras mutations were detected in 27 of 93 adenocarcinomas (29.0%), one of 61 squamous cell carcinomas (1.6%), five of 39 large-cell carcinomas (12.8%), and two of 20 adenosquamous carcinomas (10%) (P = .001). G to T transversions accounted for 71% of the mutations. There was no statistically significant difference in overall survival for all patients with K-ras mutations (median survival, 39 months) compared with patients without K-ras mutations (median survival, 53 months; P = .33). There was no statistically significant difference in overall or disease-free survival for subgroups with stage I disease, adenocarcinoma, or non-squamous cell carcinoma or for specific amino acid substitutions. The median survival time for stage II patients with K-ras mutations was 13 months, compared with 38 months for patients without K-ras mutations (P = .03).
Codon 12 K-ras mutations were more common in adenocarcinomas than in squamous cell carcinomas. For the subgroup with stage II NSCLC, there was a statistically significant adverse effect on survival for the presence of K-ras mutations. However, when the entire group was considered, the presence of K-ras mutations was not of prognostic significance in this cohort of patients with resected early-stage NSCLC.
Article: [K-ras mutation predictive significance in platinum based chemotherapeutic protocols in patients with advanced non-small cell lung cancer].[show abstract] [hide abstract]
ABSTRACT: BECKGROUND/AIM: K-ras oncogene is mutated in about 20% of lung cancer. The purpose of this study was to investigate the predictive significance for therapeutic response of K-ras mutations in advanced non-small cell lung cancer (NSCLC) patients. Bronchial aspirate samples were assessed prior to platinum-based chemotherapy start in 39 patients with stage IIIb or IV NSCLC. K-ras mutations at codons 12 and 13 were analyzed by single strand conformation polymorphisam (SSCP) and allele specific oligonucleozide hybridisation of polymerase chain reaction (PCR) of the patient's DNA present in bronchial aspirate. After two cycles of chemotherapy the patients were subjected to response evaluation. Of 39 patients 10 (25.5%) demonstrated K-ras mutations, while 29 (74.4%) patients had not. There were no significant differences between these two groups of patients with respect to baseline patient caracteristics. Partial response to the therapy had 16 (41%), no changes 14 (36%), and progressive disease 9 (23%) patients. There was a tendency to higher response rate for patients without K-ras mutations versus those with mutations, but not statistically significant (p = 0.14). There was no significant predictive value for therapeutic response of K-ras mutations for advanced non-small cell lung cancer.Vojnosanitetski pregled. Military-medical and pharmaceutical review 03/2009; 66(2):149-55. · 0.18 Impact Factor
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ABSTRACT: The ras gene family (H, K and N-ras) encodes the Ras protein, a GTPase-activating protein that regulates several signal transduction pathways including cellular proliferation and differentiation. Mutations in codons 12, 13 and 61 of the ras genes constitute one of the most frequent alterations in human cancer. In the Western Hemisphere, a low frequency of mutations in these genes has been observed in head and neck carcinomas; a higher frequency has been found in countries such as India and Taiwan. Increased protein expression is a relatively frequent event in larynx carcinomas. This study was aimed to evaluate the participation of the k-ras gene and Ras expression in 20 Mexican patients with larynx squamous carcinoma, 2 with dysplasia and 4 with normal mucosa. Samples (of 26 patients) were embedded in paraffin and immunohistochemical analysis was performed for the Ras protein, as well as amplification of the k-ras gene exon 1 (108 bp) by laser capture microdissection. Then, DNA extraction, PCR and sequencing were performed looking for possible mutation in codons 12 and 13. All patients with larynx carcinoma were men, median age 62 years. Eighty-five percent of the patients had risk factors such as smoking and/or alcohol consumption, 25% were in clinical stages I and II, and 75% in stages III and IV; 45% of the patients presented tumor recurrence or persistence. In this study, no mutations were found in codons 12 or 13 of the k-ras gene; however, protein expression was observed in 95% of the samples and a higher expression of the protein was associated with tumor recurrence or persistence, although this was not statistically significant. Unexpectedly, well-differentiated carcinomas and dysplasias presented an increase in protein expression. These results suggest that ras may be involved in early stages of larynx carcinogenesis and may be activated by other mechanisms different from mutations, such as epigenetic events.Journal of experimental & clinical cancer research: CR 04/2006; 25(1):73-8. · 1.50 Impact Factor
Article: THE ROLE OF PROTO-ONCOGENES AND STIMULATION OF GROWTH FACTOR RECEPTORS IN CANCEROGENESIS OF NON-SMALL CELL LUNG CANCER[show abstract] [hide abstract]
ABSTRACT: Non-small cell lung cancer (NSCLC) is of great interest in human pathology because its apparent aggressiveness cannot be stopped by applied treatment procedures. The lack of highly specific screening tests prevents an early diagnosis of the disease. Insidious beginning and diverse and unclear clinical picture are responsible for the fact that most cases are diagnosed at advanced stages. An increasing number of patients and a short length of survival are additional factors that make this disease an imperative in the clinical practice, while vague and mutually dependent etiological factors represent a challenge in laboratory studies of the pathogenesis.Better understanding of cancerogenesis of lung cancer will give answers to the questions like: "Which molecules are associated with response or resistance to standard treatment?" and "Which of the newly synthesized drugs with ongoing clinical trials has the best clinical response in patients?" Recent studies have shown that molecular markers associated with resistance to cisplatin-based adjuvant treatment include expression of the genes from the group ERCC1 (excision repair cross- complementation group 1) and mutation of RAS proto-oncogenes. Such research suggests that molecular investigations can guide the choice of treatment for both primary and adjuvant chemotherapy. The best example for this is patients' response to chemotherapy when inhibitors of the EGFR tyrosine kinase are applied. The future of lung cancer treatment lies in development of unconventional drugs which would be based on the biological characteristics of the tumor.Acta Facultatis Medicae Naissensis. 01/2008;