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Polymorphism in gene for microsomal epoxide hydrolase as risk factor in lung cancer
S28
Abstracts
sion for the prognosis of surgical results in patients with non small cell lung cancer (NSCLC) Polotsky B.E., Laktionov K.K., Nikulitchev L.A., Gerasimov S.S., Department of thoracic oncology, Cancer Research Center, Kashirskoye sh.,24. Moscow 115478, Russia The expression of HLA-I class superficial effector molecules may be used as the prognostic factor in NSCLC: marked expression correlates with low metastatic potential and favorable prognosis. In order to determinates expression samples were taken from 46 surgically resected tumors. The expression was not registered in 24 (52,2%) cases more widespread disease. Presented with metastases mediastinal lymphnodes among them were detected in 68,7% absent HLA-I class superficial effector molecules expression (HLA-I (-)) was noted registered in 63,2% of T1-2 cases as compared with 76,9% of T3-4 cases. 1 and 3-years survival turned to be 37% and 20,8% consequently. Marked HLA-1 class superficial effector molecules expression was noted in 22(47,8%) cases presented with less widespread disease. There were 26,9% patients with mediastinal metastases in this group: the lymph nodes were involved in 35,3% of T1-2 patients and in 11,1% of T3-4 patients. The 1 and 3-years survival rate turned to be 77,2% and 63,6% consequently - this is higher than in patients who presented not registered HLA-I class superficial effector molecules expression. These data predict more probable tumor progression in patients with HLA-I (-) and suggest indications for adjuvant therapy such cases.
Polymorphism in gene for microsomal epoxide hydrolase as risk factor in lung cancer Sùalagovicù1, J., Stubùna2, J., Habalov‡, V., Kalina1,2, I, Birosù, E. 1School of Medicine, ù Safarik University, Kosùice, Slovakia 2University Hospital, Koùsice, Slovakia New insights into lung carcinogenesis have made the study of molecular markers of risk possible in human populations in the emerging field of molecular epidemiology. Several genes involved in the metabolism of carcinogens have been found to be polymorphic in human population, and specific alleles are associated with increased risks of lung cancer. This study focuses on the polymorphic enzyme microsomal epoxide hydrolase (mEH) that are involved in the detoxification of many xenobiotics involved in the etiology of lung cancer. To investigate the role of mEH in lung carcinogenesis, the polymerase chain reaction (PCR) based genotyping assay was used to detect variant forms of mEH that confer slow and fast activity. We used this assay to screen 248 blooddonor controls and the group of patients with lung cancer (n=207). The proportion of individuals with innate slow mEH activity (homozygotes) was significantly higher in lung cancer group than in the control group (lung cancer 38 [18.4%] vs. control 16 [6.5%]. The odds ratio for homozygous slow activity versus all other phenotypes was 3.26 (95% CI 1.8-6.1) for lung cancer. We have previously shown that the polymorphism in another detoxifying enzyme Ñ GSTM1 are also associated with susceptibility to lung cancer. It is unlikely that a single gene such as mEH will be sufficient to explain lung cancer susceptibility in the absence of knowledge about other susceptibility genotypes or specific exposures. Studies of interactions with xenobiotics (e.g., smoking) or other susceptibility genotypes (e.g., GSTMI, CYP1A1) may provide the most convincing evidence for a role of mEH in cancer susceptibility. Prognosis of surgical treatment of NSCLC patients by evaluation
epidermal growth factor (EGF) and its receptor content in the tumour A. Yu. Dykhno*, O.I. Kostyleva, E.S. Gershtein, A.V. Vasilyev, N.E. Kushlinsky, B.E. Polotsky. N.N. Blokhin Cancer Research Center of RAMS, Moscow, Russia. Increasing of the survival of NSCLC patients who underwent surgical treatment is one of the important goals of lung cancer researchers. Clinico-morphological parameters are traditionally used in these trials. Experimental studies have shown that EGF, EGF-like peptides and their receptor (EGFR) would be able to discriminate more aggressive NSCLC forms. In this communication we present the results of a study of EGFR and its ligands distribution in tumour tissues of 63 NSCLC patients. EGFR and EGF-like peptides contents were evaluated by radioligand and radioreceptor techniques, respectively. The EGFR was found in 75% of the tumours and their mean level was 76.0±9.1 fmol/mg of protein. EGF-like peptides were observed in 62% of the tumours, their mean level was 1140±317 pg/mg of DNA. We have not found any correlations between EGFR and its ligands expression and disease stage, tumour size, lymph nodes involvement, and histological type of NSCLC. We have shown that I -year relapse-free survival in patients with EGFR content in the tumours of more than 50 fmol/mg of protein was lower (45%) as compared to the patients with EGFR content in tumour less than 50 fmol/mg of protein (60%; p=0,03). Also we have found decreasing of 1 -year relapsefree survival in patients with tumour phenotype EGFR+LIG+ in relation to the patients, whose tumours expressed only EGFR-ligands (0% and 61%, respectively; p=0,05). Thus, these results suppose that EGFR and its ligands are independent prognostic factors in NSCLC patients and may identify patients group with more aggressive NSCLC, who need adjuvant postoperative therapy.
Value of cytological examinations in the diagnosis of lung cancer *M. Fijalkowski, *J. Graczyk, I. Pawlowska, *M. Szmidt, M. Ciepli«nska, D. Lukasiewicz, *II Department of Tuberculosis and Lung Diseases, Lodz Hospital of Lung Diseases, Lodz, Poland The aim of the study was comparison of sputum cytology with other morphological examinations enabling microscopic confirmation of lung cancer. During period 1996-1998 cancer cells were found by various methods of morphological examinations in 871 patients aged 61,8±9,2; 703 (81%) males and 168 (19%) females. Lung cancer was diagnosed in the microscopic examinations of the following percentage of samples: sputum without bronchoscopy - 34%, postbronchoscopy sputum - 49%, bronchial washing 36%, brushing 44%, catheterization of bronchus 32%, bronchial biopsy 87%, transthoracic needle biopsy 84%. Morphological examinations revealed: squamous cell carcinoma in 38% of patients, small-cell carcinoma in 20%, adenocarcinoma in 12%, non-small cell carcinoma in 26%, cancer cells in 4%. Examination of pre-and post-bronchoscopy sputum was positive mainly for squamous cell carcinoma, respectively 64% and 58%. Among 214 patients with positive post-bronchscopy sputum in 102 (48%) patients examinations /excluding bronchial biopsy/ did not reveal cancer cells. Cytology of sputum was the only method of diagnosis of lung cancer in 13% of all cases. Cytological examinations of sputum, especially when expectorated after bronchoscopy, remains useful and valuable non-invasive diagnostic method of lung cancer. Evaluation of chest x-ray screening combined with sputum
Abstracts
sion for the prognosis of surgical results in patients with non small cell lung cancer (NSCLC) Polotsky B.E., Laktionov K.K., Nikulitchev L.A., Gerasimov S.S., Department of thoracic oncology, Cancer Research Center, Kashirskoye sh.,24. Moscow 115478, Russia The expression of HLA-I class superficial effector molecules may be used as the prognostic factor in NSCLC: marked expression correlates with low metastatic potential and favorable prognosis. In order to determinates expression samples were taken from 46 surgically resected tumors. The expression was not registered in 24 (52,2%) cases more widespread disease. Presented with metastases mediastinal lymphnodes among them were detected in 68,7% absent HLA-I class superficial effector molecules expression (HLA-I (-)) was noted registered in 63,2% of T1-2 cases as compared with 76,9% of T3-4 cases. 1 and 3-years survival turned to be 37% and 20,8% consequently. Marked HLA-1 class superficial effector molecules expression was noted in 22(47,8%) cases presented with less widespread disease. There were 26,9% patients with mediastinal metastases in this group: the lymph nodes were involved in 35,3% of T1-2 patients and in 11,1% of T3-4 patients. The 1 and 3-years survival rate turned to be 77,2% and 63,6% consequently - this is higher than in patients who presented not registered HLA-I class superficial effector molecules expression. These data predict more probable tumor progression in patients with HLA-I (-) and suggest indications for adjuvant therapy such cases.
Polymorphism in gene for microsomal epoxide hydrolase as risk factor in lung cancer Sùalagovicù1, J., Stubùna2, J., Habalov‡, V., Kalina1,2, I, Birosù, E. 1School of Medicine, ù Safarik University, Kosùice, Slovakia 2University Hospital, Koùsice, Slovakia New insights into lung carcinogenesis have made the study of molecular markers of risk possible in human populations in the emerging field of molecular epidemiology. Several genes involved in the metabolism of carcinogens have been found to be polymorphic in human population, and specific alleles are associated with increased risks of lung cancer. This study focuses on the polymorphic enzyme microsomal epoxide hydrolase (mEH) that are involved in the detoxification of many xenobiotics involved in the etiology of lung cancer. To investigate the role of mEH in lung carcinogenesis, the polymerase chain reaction (PCR) based genotyping assay was used to detect variant forms of mEH that confer slow and fast activity. We used this assay to screen 248 blooddonor controls and the group of patients with lung cancer (n=207). The proportion of individuals with innate slow mEH activity (homozygotes) was significantly higher in lung cancer group than in the control group (lung cancer 38 [18.4%] vs. control 16 [6.5%]. The odds ratio for homozygous slow activity versus all other phenotypes was 3.26 (95% CI 1.8-6.1) for lung cancer. We have previously shown that the polymorphism in another detoxifying enzyme Ñ GSTM1 are also associated with susceptibility to lung cancer. It is unlikely that a single gene such as mEH will be sufficient to explain lung cancer susceptibility in the absence of knowledge about other susceptibility genotypes or specific exposures. Studies of interactions with xenobiotics (e.g., smoking) or other susceptibility genotypes (e.g., GSTMI, CYP1A1) may provide the most convincing evidence for a role of mEH in cancer susceptibility. Prognosis of surgical treatment of NSCLC patients by evaluation
epidermal growth factor (EGF) and its receptor content in the tumour A. Yu. Dykhno*, O.I. Kostyleva, E.S. Gershtein, A.V. Vasilyev, N.E. Kushlinsky, B.E. Polotsky. N.N. Blokhin Cancer Research Center of RAMS, Moscow, Russia. Increasing of the survival of NSCLC patients who underwent surgical treatment is one of the important goals of lung cancer researchers. Clinico-morphological parameters are traditionally used in these trials. Experimental studies have shown that EGF, EGF-like peptides and their receptor (EGFR) would be able to discriminate more aggressive NSCLC forms. In this communication we present the results of a study of EGFR and its ligands distribution in tumour tissues of 63 NSCLC patients. EGFR and EGF-like peptides contents were evaluated by radioligand and radioreceptor techniques, respectively. The EGFR was found in 75% of the tumours and their mean level was 76.0±9.1 fmol/mg of protein. EGF-like peptides were observed in 62% of the tumours, their mean level was 1140±317 pg/mg of DNA. We have not found any correlations between EGFR and its ligands expression and disease stage, tumour size, lymph nodes involvement, and histological type of NSCLC. We have shown that I -year relapse-free survival in patients with EGFR content in the tumours of more than 50 fmol/mg of protein was lower (45%) as compared to the patients with EGFR content in tumour less than 50 fmol/mg of protein (60%; p=0,03). Also we have found decreasing of 1 -year relapsefree survival in patients with tumour phenotype EGFR+LIG+ in relation to the patients, whose tumours expressed only EGFR-ligands (0% and 61%, respectively; p=0,05). Thus, these results suppose that EGFR and its ligands are independent prognostic factors in NSCLC patients and may identify patients group with more aggressive NSCLC, who need adjuvant postoperative therapy.
Value of cytological examinations in the diagnosis of lung cancer *M. Fijalkowski, *J. Graczyk, I. Pawlowska, *M. Szmidt, M. Ciepli«nska, D. Lukasiewicz, *II Department of Tuberculosis and Lung Diseases, Lodz Hospital of Lung Diseases, Lodz, Poland The aim of the study was comparison of sputum cytology with other morphological examinations enabling microscopic confirmation of lung cancer. During period 1996-1998 cancer cells were found by various methods of morphological examinations in 871 patients aged 61,8±9,2; 703 (81%) males and 168 (19%) females. Lung cancer was diagnosed in the microscopic examinations of the following percentage of samples: sputum without bronchoscopy - 34%, postbronchoscopy sputum - 49%, bronchial washing 36%, brushing 44%, catheterization of bronchus 32%, bronchial biopsy 87%, transthoracic needle biopsy 84%. Morphological examinations revealed: squamous cell carcinoma in 38% of patients, small-cell carcinoma in 20%, adenocarcinoma in 12%, non-small cell carcinoma in 26%, cancer cells in 4%. Examination of pre-and post-bronchoscopy sputum was positive mainly for squamous cell carcinoma, respectively 64% and 58%. Among 214 patients with positive post-bronchscopy sputum in 102 (48%) patients examinations /excluding bronchial biopsy/ did not reveal cancer cells. Cytology of sputum was the only method of diagnosis of lung cancer in 13% of all cases. Cytological examinations of sputum, especially when expectorated after bronchoscopy, remains useful and valuable non-invasive diagnostic method of lung cancer. Evaluation of chest x-ray screening combined with sputum