Alterations of the p53 gene may lead to the production of detectable autoantibodies (p53-Abs) in cancer patients. In order to evaluate the association of p53-Abs with pleuropulmonary diseases, four groups of subjects were analyzed by ELISA for serum p53-Abs, in the framework of a molecular epidemiologic study. Two of 30 pleural malignant mesothelioma patients (MM; 6.7%) and 8/48 lung cancer patients (LC; 16.7%) were seropositive, while all 51 healthy controls (HC) were negative. Two of 55 (3.6%) at-risk controls (RC) with non-malignant respiratory diseases were positive and were not subsequently diagnosed any cancer. The difference was statistically significant between LC and RC or HC (P=0.01), but not between MM and any other group. No correlation was found with age, sex, cancer stage or histology, cigarette smoking or occupational exposure. A longer survival (not significant) was shown in seropositive LC but not in MM. p53 expression in tumor tissue was also evaluated in a subgroup of MM. In conclusion, the presence of detectable p53-Abs in serum was associated in a statistically significant proportion of cases with LC but only occasionally with MM. The longer survival among positive LC patients and the presence of two seropositive among patients with non-neoplastic respiratory diseases should be further investigated.
The glycophoryn A (GPA) assay evaluates somatic in vivo mutations. It is considered a cumulative biodosimeter for genotoxic exposures and is under evaluation in cancer risk assessment. GPA, a polymorphic membrane protein of the erythrocytes, determines the MN blood groups. The N0 and NN variant frequencies (VF) may be detected in MN subjects (about 50% of the population) by flow cytometry using two differently labelled antibodies. We explored if GPA N0 and NN VF might be relevant to the assessment of individual lung cancer risk and susceptibility, in a small population with a high prevalence of heavy tobacco smokers: 8 lung cancer patients and 16 subjects with non‐malignant lung diseases associated with increased risk of lung cancer. There was a wide interindividual variability and complete overlap between non‐neoplastic and neoplastic patients. A significant positive correlation was seen with smoking duration in N0 VF (p=0.04, age‐adjusted). Current smokers (n=12) displayed higher N0 values than never (n=1) or ex‐smokers (n=11), 36.3±18.2 and 21.0±13.2, respectively (p < 0:01). No association was shown with occupational exposure. The present exploratory study suggests that assessment of individual lung cancer risk and susceptibility by the GPA assay does not seem to be feasible. The assay appears to provide a biomarker of longterm exposure to tobacco smoke.
The role of chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC) has been a subject of debate for many years. Only recently, cisplatin-based combination chemotherapy has been demonstrated to yield a small but definite survival benefit and to improve symptoms, performance status and quality of life in a substantial proportion of advanced NSCLC patients. The cisplatin-etoposide (PE) regimen was developed in the early 1980s and has been one of the standard chemotherapy programs most extensively used in the clinical practice until a few years ago. More recently, several randomized trials have compared the efficacy of new cisplatin-containing combination chemotherapies including Paclitaxel or Gemcitabine with that of PE or PE-like regimens. Preliminary results are encouraging, indicating a small benefit in favor of the last generation of regimens which might therefore replace PE as 'gold standards' in the treatment of advanced NSCLC. However, the costs of these last generation regimens is higher and the entity of the benefit small. Therefore, PE chemotherapy can still be an option in selected situations.