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cases (environmental in 52.2%, occupational in 20.9%, and housecontact in 4.5%). Thrombocytosis was reported in 17 patients (25.4%). Median survival was 12 months (95% confidence interval[CI], 8.59 to 15.41). Presence of weight loss, thrombocytosis, and effusion; severity of effusion; PS; smoking history; duration between the beginning of symptoms and diagnosis; age; sex; and stage of disease were examined to determine the effects on survival. Cox regression and Logrank analysis were performed statistically. None of all parameters except PS showed significant effect on survival. Poor PS was associated with a poor prognosis (p = 0.01). Survival was inversely proportional to the severity of effusion (p = 0.027). There was no significant relation between duration of symptom-diagnosis, and survival. Prognosis was favorable in patients who were treated with chemotherapy (p = 0.002). As a conclusion; although PS, smoking history, and severity of effusion showed significant effect on survival estimation, duration between initial symptoms and diagnosis did not have predictive effect.
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Stop lung cancer - community aimed project
P. Berzinec, J. Dlhy. Institute of TB and Respiratory Diseases, Nitra,
Slovakia Introduction: Lung cancer incidence rate in Slovakia is approximately 80 per 100,000 for men and 12 per 100,000 for women. In the region of Nitra, with a total population exceeding 250,000, lung cancer incidence ranks among the highest in Slovakia. STOP LUNG CANCER - community aimed project was prepared by the end of 1998 as a part of Community Friendly Hospital and Health Promoting Hospital projects. Purpose: Reduction of lung cancer incidence in the region of Nitra. Methods: Interventions on 3 areas: smoking, occupational carcinogens, nutrition. The following forms of interventions were included into the project: school-based program for prevention of smoking, advice from health professionals for smoking cessation, information/motivation containing facts about smoking, known cancerogens and nutritional factors disseminated by leaflets/booklets, posters, mass media campaign, and a special web-site, total community activation. These interventions should be in part realized in cooperation with regional governmental and non-governmental institutions and organizations. Activities which have been already done: (1) information about smoking, occupational carcinogens, nutrition, and lung cancer are available in Slovak on intemet: www.viapvt.sk, or www.viapvt.sk/stoprakovinepluc.htm (2) informative posters and leaflets were installed and distributed at several places in our institution, (3) interventions (posters, leaflets, oral communications) started at 5 secondary schools and 4 primary schools, (4) information were given in the regional radio, (5) information about the project were given to all pulmonologists, several general practitioners and other specialists and health care workers in the region - most of them are supporting this project by now. Plans for future: improvement of information on internet, better involvement of regional mass-media, new edition of leaflet and poster, further activities in community. Evaluation of Results: Long-term follow-up of lung cancer incidence in Nitra.
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Co-expression of polycomb proteins EZH2 and BMI-1 in squamous cell carcinomas of the bronchus
R,H.J. Breuer 1,2, P.J.F. Snijders 2, A,P. Otte 3, F,J. v Kemenade 2, E.F. Srnit1, P.E. Postmus I , C.J.L.M. Meijer 1, F.M Raaphorst I .
Departments of 1Pulmonology; 2pathology of the University Hospital Vrije Universiteit, Amsterdam; 3EC Slater Institute, University of Amsterdam, The Netherlands Introduction: Polycomb-group (Pc-G) proteins are important regulators of embryonic development, and also contribute to regulation of the cell cycle and lymphopoiesis in the adult. Two human Pc-G protein complexes exist, one containing EZH2, the other containing BMI-I. Normally, proteins of these two complexes do not co-express in one
nucleus. However, in haematological malignancies, including large Bcell lymphomas and Hodgkin's disease, this pattern is disturbed and EZH2 and BMI-1 are colocalized in the same nucleus. This suggests that aberrant expression of EZH2 and BMI-1 complexes contribute to oncogenesis. We questioned whether deregulation of Pc-G expression also occurs in solid tumors, and investigated the immunostaining pattern of EZH2 and BMI-1 in bronchial carcinomas and adjacent normal bronchial epithelium. Materials & Methods: For this study, 7 bronchial squamous cell carcinomas resected between 1995 and 1997 were randomly chosen. Part of the tumor tissue and adjacent normal tissue was formalin fixed, the other part was snap-frozen and stored at -800 C. We investigated expression of EZH2 and BMI-I in 7 formalin fixed bronchial squamous cell carcinomas and adjacent normal bronchial epithelium using immunohistochemistry. Consecutive slides of 4 i~m were immunostained for EZH2 and BMI-1, respectively. Double immunofluorecent stainings for EZH2 and BMI-1 were performed on 4 I~m slides of the frozen counterparts. Results: Nuclei of normal bronchial epithelial cells (Ki-67 negative) showed BMI-1 expression, but absence of EZH2 immunostaining. However, 6 of the 7 carcinomas showed immunostaining of both BMi-1 and EZH2. Double immunofluorescence revealed that the tumor cells were double positive for BMI-1 and EZH2, indicating coexpression in the same nuclei. Co-expression of BMI-1 and EZH2 was also observed in dysplastic epithelium immediately adjacent to tumor fields. Conclusion: Co-expression of the Pc-G proteins BMI-1 and EZH2 may provide a marker of malignant transformation of bonchial epithelium. Whether dysregulation of the Pc-G protein complexes is etiologically involved in transformation of bronchial epithelium remains to be determined.
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immunostaining and hTERT expression in endobronchial premalignant lesions
R.H.J. Breuer 1,2, P.J.F. Snijders 2, M, Egging2, G.T. Sutedja 1, H. vd Linden2, E.K,J, Risse2, C.J,LM. Mijer2, RE. Postmus 1, E.E Smit 1,
Departments of 1Pulmonology; 2pathology, University Hospital Vrije Universiteit, Amsterdam, The Nethedands Introduction: There is a strong need for progression markers that may aid the identification of individuals at greatest risk of developing bronchial cancer by virtue of progressive premalignant lesions. In an attempt to find progression markers for premalignant bronchial disease we studied p53 alterations and expression oft he telomerase catalytic subunit hTERT. Materials & Methods: Lesions were collected during bronchoscopy of cancer free patients previously treated for tumors of the respiratory tract, using Lung Imaging fluorescence Endoscopy (LIFE). Two paired biopsies were taken at areas suspicious of of a preneoplastic lesion. One biopsy was formalin fixed and used for p53 immunohistochemistry (n = 46) the other was snap-frozen and used to determine hTERT mRNA levels by semiquantitative RT-PCR (n = 54). Samples were catagorized into 5 groups: normal, hyperplasia and squamous metaplasia (N/H/S), mild dysplasia (M), moderate dysplasia (MD), severe dysplasia (SD) and Carcinoma in Situ (CIS). Normal (N) samples were removed from the group (N/H/S) for p53 immunostainings. Three catagories were defined for p53 immunostaining profiles: negative (N), nuclear staining confined to the basal cell layer (B) and suprabasal staining (SB). Results: Suprabasal p53 staining occurs significantly more frequent in SD and CIS compared to H/S (p < 0.001). hTERT mRNA levels were significantly higher in CIS compared to HIS (p = 0.021). hTERT levels were significantly higher in samples with SB p53 immunostaining compared to samples with B p53 staining (p = 0.014). Conclusion: p53 alterations manifested by SB p53 immunostaining seems to procede elevated hTERT mRNA levels during bronchial carcinogenesis. SB p53 immunostainings and hTERT mRNA in addition to the histology might be of value to identify progressive premalignant lesions.