- Email: [email protected]
640 Survival of resected patients with small cell lung cancer (SCLC) according to CaMBr1 tumor-associated antigen
164
l-l639
Biology Usage of PCR-SSCP in the detection of P53 gene mutation in preserved sputum for the diagnosis of lung cancer
experimental therapt in MM is therefore difficult. Using tumor markers we hope to detect patients with a poor prognosis or early progression during the treatment. During cell division and cell death in different tumors, cytokeratin fragments are excreted in the blood. Cyfra 27-7 (Centocor, Malvern, USA) uses two monoclonal antibodies (Moabs) to measure cytokeratin fragment 19 and TPA-M (Tissue Polypeptide Antigen, Santec, Medical, Bromma, Sweden) uses three Moabs to measure cytokeratin fragments 8,18 and 19. In a series patients presenting with MM several prognostic variables were investigated in a prospective manner using Cox multivariate analysis. In some patients, treated with experimental chemotherapy, the tumor markers were followed prospectively. Results: of 52 patients entered, 48 had died (mean survival of 335 days, range 17-1826). Of 12 prognostic factors (tumor type, stage, performance, gender, age, pain, weight loss, thrombocytosis, asbestos exposure, Cyfra 21-1, TPA-M and smoking) only PS, Cyfra 21-l and TPA-M were significant for survival (p-values 0.0011, 0.0088 and 0.0098 resp.). The values for Cyfra 21-l were 0.1-258 (mean 14.9 pmol/l, cut off at 1.2) and for TPA-M 23-3593 (mean 334 U/l, cut off at 80). After correction for Cyfra 21-l no other significant factor could be found in this patient group..In a few patients the tumor markers were measured during experimental therapy. The clinical disease status correlated well with both Cyfra 21-l and TPA-M but in only one patient a positive lead time could be found. Conclusions: In this group of patients with MM these tumor markers had some prognostic value and can monitor disease progression in MM.
Li Logyun, Cao Lejie, Guo Zijian, Zhu Yuanjue. Deparfment of Respiratory Diseases, Peking Union Medical College Hospital CAMS and PUMC, Beijing, PR China
Objective: To screen for P53 abnormalities of sputum samples in patients with lung cancer and investigate its probable value in early diagnosis of lung cancer. Material and Methods: The improved Saccomanno’s concentration method was carried in preserved sputum samples and the polymerase chain reaction-single strand confom7ation polymorphism (PCR-SSCP) analysis was used for P53 gene investigation. By examining 22 sputum samples (15 from confirmed lung cancer patients, 5 from clinically suspected lung cancer patients, 1 from sarcoidosis patient and 1 from right central pneumonia patient) and normal lung tissue as control. Results: We found 10 in 22 patients have positive tumor cells and the mean DNA concentration of preserved sputum samples is 1.88 & 1.49 mg/ml, OD260 nrnIOD280 nm ratio is 1.61. Eight (40%) preserved sputum specimens (6 from 15 confirmed lung cancer patients, 2 from 5 clinically suspected lung cancer patients without pathologic evidences) have been found P53 gene abnormalities. Two non-lung tumor sputum samples and one normal lung tissue haven’t been found any P53 gene abnormality. Conclusion: It is concluded that the preserved sputum samples of the improved Saccomanno’s method is a very important pretreatment for P53 gene investigation. PCR-SSCP analysis of sputum sampled is successful in detection of P53 gene abnormalities in lung cancer patients and may be used as one of the methods for gene diagnosis of lung cancer. For advanced study, may be it could be used to screen and survey high risk lung cancer patients.
640 El
Survival of resected patients with small cell lung cancer (SCLC) according to CaMBrl tumor-associated antigen
A. Favaretto ’ , S. Menard 2, A. Paccagnella ’ , F. Sartori 3, S. Fasolato ’ , R. Veggian ’ , S. Garbisa ‘, F. Oniga’ , M.V. Fiorentino ’ Departments of ’ Medical Oncology; 3 Thoracic Surgery; Azienda Ospedalieta, Padova; 2/sfifufo Nazionale Tumori, Milano, 1-35128, Italy CaMBrl isacell surface antigen with asuggested prognostic significance in patients with SCLC. At the moment surgery in SCLC patients is considered a standard option for stage I and II disease and experimental in stage Illa. We retrospectively analyzed the survival of 45 operated patients with SCLC in relation to CaMBrl positivity evaluated with immunohistochemistry in paraffin sections from surgical specimens. The 45 patients received also CAV/PE as adjuvant, for stage I-II pts, and as induction chemotherapy for stage Illa. Radiotherapy was delivered to stage llla patients having residual disease after surgery. The median age was 60; 41 were males; 43 patients had PS > 70%; 11 (24%) patients had weight loss; 18 (40%) had an elevated LDH; 20 patients were stage I, 9 stage II, and 16 stage Illa. 32 patients died and 13 are alive; the overall median estimated survival is 25 months with a 3-yr and a 5-yr survival of 33.8% and 28.3%. Seventeen patients were CaMBrl(+) and 28 CaMBrl(-). The Kaplan-Meier survival at 3 yrs was respectively 11.8% in the 17 CaMBrl(+) and 47.7% in the 28 negative; the 5-yr survival respectively was 0% and 42.4% (p < 0.0008). With Cox multivariate analysis the CaMBrl factor was the strongest survival predictor, independent from all the other relevant prognostic factors (p < 0.0025). The possibility to clearly identify stage I and II patients with poor long-term life expectancy [CaMBrl(+)] could allow a significant proportion of them to avoid unnecessary surgery.
16411 Tumor markers in malignant usefulness
mesothelioma
P. Baas, J.H. Schouwink, C.M. Korse, J.M.G. Bonfrer. Cancer Institute, Amsterdam, The Netherlands
-Their
The Netherlands
For Malignant Mesothelioma (MM) no standard treatment has so far been found. Many phase I and II trials, using chemotherapeutic regimens, are initiated in order to improve survival. The diffuse pleural thickening makes it difficult to find measurable target lesions. Assessment of the response to
I
642
Expression of lysosomal bronchogenic cancer
H. Neef, E. Weber’ , H. Kirschke’, Surgery; ’ lnsfifufe of Physiological Hal/e- Wittenberg, Germany
proteinases
M. Meyer. Chemist%
in
Dept. of Cardiofhomcic Martin-Luther-University
Activity and concentration of extracellular proteolytic enzymes have been shown to be elevated in malignant tumors. The pattern of different cathep sins and its relationship to histological type, grade and stage of lung cancer have not been evaluated intensively so far. Methods: Activities of cathepsins B, C, H, L (lysosomal cysteineproteinases) and cathepsin D (lysosomal aspartateproteinase) were analyzed in cancer and normal lung tissue in 80 cases. (36 squamous cell, 20 adeno, 6 adenosquamous, 18 other histologies). Because enzyme concentration measurement allows determination of overexpression (including inactive procathepsins), additional Elisa-analysis was performed for cathepsins L and S. Results: Mean activity values of cathepsins L, B, H, C were significantly higher (3 times) in cancer tissue compared to lung parenchyma. Cathepsin D was not elevated. Expression of cathepsins L and H was higher in squamous cell compared to adenocarcinoma, but reverse for cathepsin B and C. Highest values of cathepsin Land C were found in adenosquamous carcinoma but this was not true for B and H. There was no correlation of cathepsin activities with differentiation (grade) and stage of the tumors. There were higher concentrations of cathepsin L (480 ng/mg protein) and cathepsin S (636 ng/mg protein) compared to lung parenchyma (170 ng/mg and 314 ng/mg protein). Conclusion: Cathepsin activity is increased in lung cancer tissue compared to lung parenchyma. There are different patterns of cathepsin activity according to histological types, but no correlation to grade of differentiation and TNM-stage of lung cancer. Clinical importance of these results will be discussed.
~16, RB, p63 and cyclin Dl expression and hypermethylation of plG/CDKN2 gene in thymoma and thymic carcinoma H. Hirabayashi ’ , Y. Fujii ‘, Masahiro Sakaguchi 3, H. Tanaka ‘, H.-E. Yoon ‘, S. Takeda’, Hikaru Matsuda’. ’ ls’Depf. of Surg. Osaka Univ. Med. Sch., Osaka; ‘2nd Depf of Surg. Nagoya Cify Unix Med. Sch. Nagoya, Japan, 3Simmons Cancer Cfr., Univ of Texas Southwestern Med. Cfr, Da//as, USA Till now, although several clinicopathological and immunological studies of thymoma have been reported, little is known of the genetic alterations that occur in the tumorigenesis of thymomas. To investigate the expression of ~16, pRB, ~53, and cyclin Dl in thymomas, we examined 36 thymomas
l-l639
Biology Usage of PCR-SSCP in the detection of P53 gene mutation in preserved sputum for the diagnosis of lung cancer
experimental therapt in MM is therefore difficult. Using tumor markers we hope to detect patients with a poor prognosis or early progression during the treatment. During cell division and cell death in different tumors, cytokeratin fragments are excreted in the blood. Cyfra 27-7 (Centocor, Malvern, USA) uses two monoclonal antibodies (Moabs) to measure cytokeratin fragment 19 and TPA-M (Tissue Polypeptide Antigen, Santec, Medical, Bromma, Sweden) uses three Moabs to measure cytokeratin fragments 8,18 and 19. In a series patients presenting with MM several prognostic variables were investigated in a prospective manner using Cox multivariate analysis. In some patients, treated with experimental chemotherapy, the tumor markers were followed prospectively. Results: of 52 patients entered, 48 had died (mean survival of 335 days, range 17-1826). Of 12 prognostic factors (tumor type, stage, performance, gender, age, pain, weight loss, thrombocytosis, asbestos exposure, Cyfra 21-1, TPA-M and smoking) only PS, Cyfra 21-l and TPA-M were significant for survival (p-values 0.0011, 0.0088 and 0.0098 resp.). The values for Cyfra 21-l were 0.1-258 (mean 14.9 pmol/l, cut off at 1.2) and for TPA-M 23-3593 (mean 334 U/l, cut off at 80). After correction for Cyfra 21-l no other significant factor could be found in this patient group..In a few patients the tumor markers were measured during experimental therapy. The clinical disease status correlated well with both Cyfra 21-l and TPA-M but in only one patient a positive lead time could be found. Conclusions: In this group of patients with MM these tumor markers had some prognostic value and can monitor disease progression in MM.
Li Logyun, Cao Lejie, Guo Zijian, Zhu Yuanjue. Deparfment of Respiratory Diseases, Peking Union Medical College Hospital CAMS and PUMC, Beijing, PR China
Objective: To screen for P53 abnormalities of sputum samples in patients with lung cancer and investigate its probable value in early diagnosis of lung cancer. Material and Methods: The improved Saccomanno’s concentration method was carried in preserved sputum samples and the polymerase chain reaction-single strand confom7ation polymorphism (PCR-SSCP) analysis was used for P53 gene investigation. By examining 22 sputum samples (15 from confirmed lung cancer patients, 5 from clinically suspected lung cancer patients, 1 from sarcoidosis patient and 1 from right central pneumonia patient) and normal lung tissue as control. Results: We found 10 in 22 patients have positive tumor cells and the mean DNA concentration of preserved sputum samples is 1.88 & 1.49 mg/ml, OD260 nrnIOD280 nm ratio is 1.61. Eight (40%) preserved sputum specimens (6 from 15 confirmed lung cancer patients, 2 from 5 clinically suspected lung cancer patients without pathologic evidences) have been found P53 gene abnormalities. Two non-lung tumor sputum samples and one normal lung tissue haven’t been found any P53 gene abnormality. Conclusion: It is concluded that the preserved sputum samples of the improved Saccomanno’s method is a very important pretreatment for P53 gene investigation. PCR-SSCP analysis of sputum sampled is successful in detection of P53 gene abnormalities in lung cancer patients and may be used as one of the methods for gene diagnosis of lung cancer. For advanced study, may be it could be used to screen and survey high risk lung cancer patients.
640 El
Survival of resected patients with small cell lung cancer (SCLC) according to CaMBrl tumor-associated antigen
A. Favaretto ’ , S. Menard 2, A. Paccagnella ’ , F. Sartori 3, S. Fasolato ’ , R. Veggian ’ , S. Garbisa ‘, F. Oniga’ , M.V. Fiorentino ’ Departments of ’ Medical Oncology; 3 Thoracic Surgery; Azienda Ospedalieta, Padova; 2/sfifufo Nazionale Tumori, Milano, 1-35128, Italy CaMBrl isacell surface antigen with asuggested prognostic significance in patients with SCLC. At the moment surgery in SCLC patients is considered a standard option for stage I and II disease and experimental in stage Illa. We retrospectively analyzed the survival of 45 operated patients with SCLC in relation to CaMBrl positivity evaluated with immunohistochemistry in paraffin sections from surgical specimens. The 45 patients received also CAV/PE as adjuvant, for stage I-II pts, and as induction chemotherapy for stage Illa. Radiotherapy was delivered to stage llla patients having residual disease after surgery. The median age was 60; 41 were males; 43 patients had PS > 70%; 11 (24%) patients had weight loss; 18 (40%) had an elevated LDH; 20 patients were stage I, 9 stage II, and 16 stage Illa. 32 patients died and 13 are alive; the overall median estimated survival is 25 months with a 3-yr and a 5-yr survival of 33.8% and 28.3%. Seventeen patients were CaMBrl(+) and 28 CaMBrl(-). The Kaplan-Meier survival at 3 yrs was respectively 11.8% in the 17 CaMBrl(+) and 47.7% in the 28 negative; the 5-yr survival respectively was 0% and 42.4% (p < 0.0008). With Cox multivariate analysis the CaMBrl factor was the strongest survival predictor, independent from all the other relevant prognostic factors (p < 0.0025). The possibility to clearly identify stage I and II patients with poor long-term life expectancy [CaMBrl(+)] could allow a significant proportion of them to avoid unnecessary surgery.
16411 Tumor markers in malignant usefulness
mesothelioma
P. Baas, J.H. Schouwink, C.M. Korse, J.M.G. Bonfrer. Cancer Institute, Amsterdam, The Netherlands
-Their
The Netherlands
For Malignant Mesothelioma (MM) no standard treatment has so far been found. Many phase I and II trials, using chemotherapeutic regimens, are initiated in order to improve survival. The diffuse pleural thickening makes it difficult to find measurable target lesions. Assessment of the response to
I
642
Expression of lysosomal bronchogenic cancer
H. Neef, E. Weber’ , H. Kirschke’, Surgery; ’ lnsfifufe of Physiological Hal/e- Wittenberg, Germany
proteinases
M. Meyer. Chemist%
in
Dept. of Cardiofhomcic Martin-Luther-University
Activity and concentration of extracellular proteolytic enzymes have been shown to be elevated in malignant tumors. The pattern of different cathep sins and its relationship to histological type, grade and stage of lung cancer have not been evaluated intensively so far. Methods: Activities of cathepsins B, C, H, L (lysosomal cysteineproteinases) and cathepsin D (lysosomal aspartateproteinase) were analyzed in cancer and normal lung tissue in 80 cases. (36 squamous cell, 20 adeno, 6 adenosquamous, 18 other histologies). Because enzyme concentration measurement allows determination of overexpression (including inactive procathepsins), additional Elisa-analysis was performed for cathepsins L and S. Results: Mean activity values of cathepsins L, B, H, C were significantly higher (3 times) in cancer tissue compared to lung parenchyma. Cathepsin D was not elevated. Expression of cathepsins L and H was higher in squamous cell compared to adenocarcinoma, but reverse for cathepsin B and C. Highest values of cathepsin Land C were found in adenosquamous carcinoma but this was not true for B and H. There was no correlation of cathepsin activities with differentiation (grade) and stage of the tumors. There were higher concentrations of cathepsin L (480 ng/mg protein) and cathepsin S (636 ng/mg protein) compared to lung parenchyma (170 ng/mg and 314 ng/mg protein). Conclusion: Cathepsin activity is increased in lung cancer tissue compared to lung parenchyma. There are different patterns of cathepsin activity according to histological types, but no correlation to grade of differentiation and TNM-stage of lung cancer. Clinical importance of these results will be discussed.
~16, RB, p63 and cyclin Dl expression and hypermethylation of plG/CDKN2 gene in thymoma and thymic carcinoma H. Hirabayashi ’ , Y. Fujii ‘, Masahiro Sakaguchi 3, H. Tanaka ‘, H.-E. Yoon ‘, S. Takeda’, Hikaru Matsuda’. ’ ls’Depf. of Surg. Osaka Univ. Med. Sch., Osaka; ‘2nd Depf of Surg. Nagoya Cify Unix Med. Sch. Nagoya, Japan, 3Simmons Cancer Cfr., Univ of Texas Southwestern Med. Cfr, Da//as, USA Till now, although several clinicopathological and immunological studies of thymoma have been reported, little is known of the genetic alterations that occur in the tumorigenesis of thymomas. To investigate the expression of ~16, pRB, ~53, and cyclin Dl in thymomas, we examined 36 thymomas