Lung function predicts lung cancer risk in smokers: a tool for targeting screening programmes.

The relationship between smoking, lung cancer and airflow obstruction is recognised but it is unclear whether the presence of minimal lung function damage constitutes an independent risk factor for the development of lung cancer. In order to identify those individuals at higher risk of lung cancer on the basis of functional impairment, we evaluated baseline pulmonary function tests of 3,806 heavy smokers undergoing annual chest computed tomography screening, and compared the forced expiratory volume in 1 s (FEV(1)) % predicted of 57 lung cancer cases and that of 3,749 subjects without cancer. We obtained odds ratios (ORs) of lung cancer and the corresponding 95% confidence intervals (CIs) using unconditional logistic regression, adjusting for age, sex, study and smoking variables. Compared with subjects with FEV(1) >or=90% pred, the OR of lung cancer was 2.45 (95% CI 1.39-4.33) for subjects with FEV(1) <90% pred and 2.90 (95% CI 1.34-6.27) for subjects with FEV(1) <70% pred. These data show that even a relatively small reduction in FEV(1) % pred is a significant predictor of increased lung cancer risk. Test screening for lung cancer using airflow obstruction with FEV(1) <90% is a strategy worth future consideration.

Prognostic value of immunohistochemical expression of p53, bax, Bcl-2 and Bcl-xL in resected non-small-cell lung cancers.

AIMS: Some experimental evidence suggests that in lung cancer, development, progression and an increased proliferation rate can be linked to apoptosis-related factors. In this study we evaluated the possible role of p53 and Bcl-2 gene family members as prognostic factors for non-small-cell lung cancer. METHODS AND RESULTS: We investigated the immunohistochemical expression of p53 and Bcl-2 gene family members (bax, Bcl-2 and Bcl-xL) in 94 non-small-cell lung cancer specimens to establish the role of these genes in lung cancer pathogenesis, and to evaluate their prognostic importance. The expression of Bcl-2 was correlated with a shorter patient survival time and with the nodal status of the neoplasm. We also found frequent over-expression of bax and Bcl-xL to be of no prognostic significance. Finally, we found no correlation between frequent detection of aberrant p53 protein and expression of either Bcl-2, bax or Bcl-xL or with patient survival time. CONCLUSIONS: This study confirms a relevant role for apoptosis-regulatory proteins in the pathogenesis of lung cancer, and highlights the possible role of Bcl-2 as a prognostic factor for this tumour.

Expression of p21 in SV40 large T antigen positive human pleural mesothelioma: relationship with survival.

BACKGROUND: Mesothelioma is the most commonly occurring primary pleural neoplasm. Several studies have documented an increase in the incidence of this malignancy during the last decades. Although the association between asbestos exposure and development of mesothelioma is generally accepted, the exact mechanism of carcinogenesis is unknown. Recently, Simian virus 40 large T antigen (SV40 Tag) expression has been detected in pleural mesothelioma. The ability of SV40 oncoproteins to inactivate p53 and retinoblastoma tumour suppressor proteins has been proposed as an important step in the pathogenesis of human mesothelioma. METHODS: To obtain a better understanding of the molecular mechanisms of the pathogenesis of mesothelioma, the expression of the cell cycle inhibitor p21(WAF1/CIP1) (p21), a downstream target of p53, was evaluated immunohistochemically in a group of 29 mesothelioma specimens already characterised for the presence of SV40 Tag sequences. RESULTS: Statistical analysis did not reveal any correlation between p21 expression and histopathological type of mesothelioma using the kappa(2) test (p=0.577). A significant positive relationship was found between p21 expression level and the patients' overall survival according to the Kaplan-Meier survival curves and using a log rank test (median difference in survival 7 months, 95% CI 4.8 to 9.9; p<0.001). CONCLUSIONS: Determination of p21 expression bears a prognostic significance in patients affected with mesothelioma, further underlining the role of SV40 in the pathogenesis of malignant pleural mesothelioma.

Evidence of a restrictive spirometric pattern in older thalassemic patients.

BACKGROUND: Lung impairment represents one of the complications of thalassemia major whose clinical picture can remain in subclinical form all life long. Few works have been published and the results are contradictory. OBJECTIVES: The aim of this study was to determine the spirometric pattern, the age of onset in thalassemic boys and girls, and to investigate the association with the onset of endocrinological complications. METHODS: We studied 48 patients, divided into three groups according to pubertal stages, in order to better distinguish the periods of life in which different endocrinological complications usually appear. Group A: (n = 14; 8 F, 6 M; age 10.8 +/- 1.7 years): prepubertal patients; group B (n = 21; 10 F, 11 M; age 15.7 +/- 1.1 years): pubertal patients; and group C (n = 13; 9 F, 4 M; age 19.0 +/- 1.4 years): postpubertal patients. Pulmonary function tests (PFTs) and diffusing capacity for carbon monoxide (DCO), corrected for both Hb values (DCO*) and alveolar volume (KCO), were performed 2 days after blood transfusion and were considered pathologic when they fell below 80% of the predicted value. RESULTS: All patients in group A showed normal PFTs, DCO* and KCO values, as well as normal endocrinological assessment. By contrast, all those in group C showed a restrictive spirometric pattern with reduced DCO* (63 +/- 8%), elevated KCO values (120 +/- 14%), a variable degree of hypoxia (PO2 82 +/- 9%), and high serum ferritin levels. Only 2 patients showed a radiological picture of interstitial fibrosis. Furthermore, 9 patients had hypogonadism and 3 hypothyroidism. In group B, only 3 patients showed a restrictive pattern and 1 of them reduced DCO* values, and 2 out of 3 patients had hypogonadism. Considering all patients on the whole, DCO* was negatively correlated with both serum ferritin (r = -0.58; p < 0.05) and age (r = -0.57; p < 0.05). CONCLUSIONS: The presence of a restrictive pattern in 16 older patients associated with both high serum ferritin levels and endocrinological complications in a lot of them was the main feature in this study. Iron overload might be the main factor determining lung impairment, even though a more accurate evaluation is necessary. Possible pathological mechanisms and the role of the genotype are discussed.

A model of BAX gene delivery to human lung cancer.

In this report we have investigated the effects of BAX in enhancing apoptosis in two primary non-small cell lung cancer cell lines. A count of the apoptotic cells by TUNEL staining revealed that almost 70% of BAX over-expressing cells died, while very few apoptotic cells were detectable in the wildtype cells or in the cells transfected with an empty vector. These findings suggest that de-regulated expression of BAX may provide a novel mechanism for initiating cell death in non-small cell lung cancer cells. Further studies are needed to better define the involvement of this protein in the complex mechanism of lung carcinogenesis and to definitely demonstrate the therapeutic utility of targeting this pathway.