RESUMO
PURPOSE: To determine the incidence of c-myc amplification and p53 mutations in patients with stage I, II and III of histologically confirmed non-small cell lung cancer (NSCLC) of different histological subtypes: adenocarcinomas (AC), squamous cell carcinomas (SCC), large cell carcinomas (LCC) and adeno-squamous carcinomas (AC-SCC) and of histological grade (G) 2 and 3. MATERIALS AND METHODS: DNA was isolated from 41 frozen tumor samples by standard phenol-chloroform extraction. Amplification of c-myc gene was determined by the differential polymerase chain reaction (PCR) method, followed by polyacrylamide gel electrophoresis, and mutations in exons 5, 6, 7 and 8 p53 gene were detected by the PCR single-strand conformation polymorphism (SSCP) method. RESULTS: c-myc gene amplification was found in 2 of 41 (4.9%) analyzed tumors and both amplifications were found in stage III tumors. Mutations in the p53 gene were found in 19 of 41 (46.3%) of the analyzed tumors. SCC and LCC were more likely to contain mutations in p53 gene (68.4% and 66.7%, respectively). CONCLUSION: Our results indicate that p53 mutations are common in NSCLC with higher incidence in SCC compared with other histological subtypes. Since the mutations are more frequent in early-stage NSCLC, it appears that mutations in p53 gene could be an early event in lung carcinogenesis. On the other hand, c-myc amplification is a rare event in NSCLC and occurs in the late phase of development of this type of lung cancer.
RESUMO
PURPOSE: The group of completely resected stage IIIa- N2 non small cell lung cancer (NSCLC) patients is considered heterogeneous in various aspects including survival and pattern of recurrence. The prognostic factors still remain controversial. Clinical trials dealing with multimodal strategy for N2 NSCLC are being watched with keen interest, and the feasibility of this strategy is to be confirmed. In the present study we attempted to clarify the role of different clinicopathological factors which separate patients into high and low- risk groups based on the disease-free and overall survival. PATIENTS AND METHODS: The study comprised 60 consecutive patients with pathologically (p) proven N2 NSCLC who had undergone complete surgical disease resection with curative intent between January 1997 and September 2000. All patients had an apparently resectable disease at preoperative staging and thoracotomy. Extensive mediastinal lymph node dissection was performed when possible and consisted of removal of all ipsilateral mediastinal lymph nodes. Patients were submitted to postoperative split course adjuvant radiotherapy. Cumulative survival rates were calculated by the Kaplan-Meier method. The analyzed prog- nostic factors were age, histological type and grade of differentiation, clinical (c) stage, cN status and tumor size and were tested for statistical significance by univariate analysis using log-rank test and Willcoxon test. RESULTS: The median follow-up period was 36 months (range 24-72 months). Tumor size, cN status and age were significant predictors of survival. Large tumor size (T3) was significantly worse predictor compared to T1 (p=0.046) and cN2 status evaluated by computed tomography (CT= also showed statistically significant unfavorable prognosis in comparison with cN0 and cN1 (p=0.0185). Patients over 65 years had significantly worse prognosis compared to those under 65 years (p=0.008). CONCLUSION: This study identified stage IIIa - N2 NSCLC prognostic subgroups and suggests different therapeutic approach according to the subgroup profile.
