The p53 alteration is the most common alteration found in human cancer. It usually involves missense mutations that stabilize the p53 protein, which in turn accumulates, reaching levels detectable by immunohistochemistry. We and others have demonstrated that this overexpression of mutant p53 protein can induce a specific humoral response in cancer patients. This result was assessed by the presence of p53 antibodies in sera of patients with various types of cancers, whereas normal populations do not exhibit such antibodies. In lung cancer, the prevalence of p53 antibodies is high (30%) and is correlated with a very high rate of p53 mutations in this cancer (60-70%). We show that these antibodies are always present at the time of diagnosis, but never appear during tumour development, an observation strengthened by the fact that these antibodies are mostly IgG, corresponding to a secondary immune response. These results suggest that the humoral response is an early event and that p53 antibodies can be used as a precocious marker of p53 alteration before clinical manifestation of the disease.

Although declining, gastric cancer (GC) is estimated to be second in frequency worldwide. Major causes appear to be environmental rather than genetic. A relationship has been suggested between tobacco smoking and GC. A number of epidemiological studies have been performed dealing with this question. All the cohort studies showed a significantly increased risk of GC of the order of 1.5-2.5 for cigarette smokers. Evidence from case-control studies is less consistent. We have carried out a meta-analysis on the 40 studies providing a quantitative estimate of the association between GC risk and tobacco smoking. Results suggest a risk of stomach cancer among smokers of the order of 1.5-1.6 as compared to non-smokers. The summary relative risk was higher in men (1.59) than in women (1.11). Several studies examined the dose-response relationship which existed in 4 cohort studies and 6 case-control studies. We estimated the number of GC cases attributable to tobacco smoking occurring worldwide: in total, over 80,000 cases of GC (11% of all estimated cases) may be attributed to tobacco smoking each year. This figure is larger than that estimated for other cancers for which association with tobacco smoking is clearly established, such as pancreatic and renal cancers. In recent decades, gastric cancer (GC) incidence has declined markedly in most of the industrialized world. However, GC is estimated to be second in frequency worldwide, and remains (although declining) the most common cancer in developing countries. The absolute number of these tumors might increase in many countries because more such cancers can be expected as people live longer. Although mortality rates have declined in parallel with incidence rates, survival has not improved, and GC remains the leading cause of cancer mortality in several countries.The rapidly declining mortality rates of GC as well as the large geographic variations in incidence, along with the decreased risk among migrants from high-risk to low-risk areas, and its higher occurrence in the lower social classes, suggest that the major causes of gastric cancer are environmental rather than genetic. Exposures early in life seem to play an important role in the development of gastric cancer, but their nature is not wellunderstood. Among the most widely accepted risk factors are a diet poor in fresh fruits and vegetables and rich in salt and chronic Helicobacter pylori infection.GC should not be considered as a single entity. Two major types can be distinguished according to subsite of occurrence: carcinoma of the corpus and carcinoma of the cardia, which arises immediately beneath the esophagogastric junction. Cancer of the cardia is suspected to represent a separate etiological and pathological entity, with a stronger male predominance, and an increasing incidence in the US and Europe where it represents 5-10% of all GC.Two main types can also be identified according to the classic histological Lauren classification: diffuse and intestinal cancer. They show different time trends and may have ...

The cause of pleural effusion was studied in 300 consecutive patients by clinical examination and laboratory tests. The three most common causes were found to be cancer 117 cases (metastatic 65, bronchogenic Pleural effusion represents a very common diagnostic problem. In all studies on the causes of this condition, apart from those that are evident, such as congestive heart failure and cirrhosis, the percentage of undetermined causes is still around 20%, even after complete diagnostic evaluation.We determined the origin of pleural effusion in patients with subacute or chronic conditions admitted to a department of thoracic diseases. The purpose of this study was to determine the specific cause-malignancy or tuberculous or bacterial infection-and ResultsThe most frequent causes of pleural effusion were cancer (39%), tuberculous infection (17 6%), and bacterial infection (126%): 20f6% were undiagnosed, and other causes represented 10% (table 1).

Summary Antibodies specific for human p53 were analysed in sera of lung cancer patients. We detected p53 antibodies in the sera of 24% (10/42) of patients with lung carcinoma. The distribution was as follows: 4/9 small-cell lung carcinomas (SCLCs), 2/18 squamous cell lung carcinomas (SCCs), 2/10 adenocarcinomas (ADCs) and 2/5 large-cell lung carcinomas (LCCs). p53 antibodies were always present at the time of diagnosis and did not appear during progression of the disease. Using an original peptide-mapping procedure, we precisely localised the p53 epitopes recognised by p53 antibodies. Immunodominant epitopes reacting with antibodies were localised in the amino and carboxy termini of the protein, similar to those found in breast carcinoma patients or in animals immunised with p53. In light of these data, we suggest that p53 antibodies occur via a self-immunisation process that is the consequence of p53 accumulation in tumour cells. p53 antibodies were also detected in two patients without detected malignant disease. One of these patients died 6 months later of lung carcinoma, suggesting that p53 antibodies may be a precocious marker of p53 alteration.

E Ex xp po os su ur re e tto o e en nv vi ir ro on nm me en nt ta al l t to ob ba ac cc co o s sm mo ok ke e a an nd d r ri is sk k o of f l lu un ng g c ca an nc ce er r: : t th he e e ep pi id de em mi io ol lo og gi ic ca al l e ev vi id de en nc ce e A number of epidemiological studies have been published since then, and have confirmed this association. The possibility of positive results due to bias has been envisaged; it seems, however, that such bias could not explain the whole excess of lung cancer. Few data are available on confounders, such as diet and previous history of lung disease, that might be responsible for the association; however, there is no evidence that they play an important role. Moreover, the biological plausibility of a causal association is supported by the similarity of the composition of ETS and active smoke.The causal association between ETS exposure and lung cancer now seems wellestablished; however, its public health impact is still debated. Estimates are available from the United States, Canada, Australia, New Zealand and England.