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Altered cJun expression: An early event in human lung carcinogenesis
140
Abstracts
/L.tatg
Cancer
I5 (19%)
139-157
be involved in lung carcinogenesis by activating carcinogens contained in tobacco smoke. Therefore, lung cancer risk should depend on both smoking exposure and CYPZD6 activity. The extent to which CYP2D6 activity, determined by using dextromethorphan, could modify the effectoftobaccowasevaluated fromastudyon 128 lung cancers and 157 controls. A strong interaction was observed; the effect of tobacco on lung cancer risk rose with increasing CYP2D6 activity (P < 0.001). Increasing levels of smoking increased lung cancer risk only among smokers with the highest CYP2D6 activity, and CYP2D6 was a risk factor only among heavy smokers. Smokers with both the highest CYP2D6 activity and daily tobacco consumption were at very high risk for lung cancer. These results may explain discrepant results of previous studies on the association between CYPZD6 activity and lung cancer.
obtained from autopsies was used as a control. In 31 patients, a synchronous or metachronous carcinoma was present (61%). Positive p53 immunoreactivity was found in 22 of the 51 patients (43 W). The positive predictive values of ~53 and of a high grade of dysplasia for carcinoma of the respiratory tract were 91% and 8096, respectively. Although the hyperproliferative state of squamous metaplastic lesions was clearly established, neither the percentage of MIB-1 labelling nor themitoticindexdistinguishedpatientgmupswithandwithoutcaminoma. No increased Bcl-2 immunostaining was found in squamous metaplasia. In conclusion, p53 immunoreactivity in squamous metaplastic lesions in bronchial biopsies is a marker of carcinoma of the respiratory tract.
Altered cJun expression: An early event in human lung carcinogenesis
Smith AL, Hung J, Walker L, Rogers TE, Vuitch F, Lee E, Gazdar AF. Simmons Cancer Center, Vniv TxSouthwestem Med CtrDallas, 5323 Harry Hines Blvd. Dallas, TX 75235-8593. Br I Cancer 1996;73:2039. According to the field cancerisation theory the entire upper aerodigestive tract has been mutagenised, thereby placing the affected individual at risk for the development of one or more cancers. To investigate this concept we studied the respiratory epithelium in lungs bearing cancer, including bronchi, bmnchioles and alveoli. After identifying preneoplastic and preinvasive lesions by light microscopy, we determined the DNA content of their nuclei in Feulgen-slained sections using a high-performance digitised image analyser. Archival material from 35 resected cases of non-small-cell lung cancer (NSCLC) was selected, including 16 central rumours (mainly squamous cell carcinomas) and 19 peripheral tumours (mainly adenocarcinomas) and five resected cases of metastatic tumour from extrathoracic primary sites. Of the NSCLCs, 3 l/35 (89 W) were aneuploid, as were 60 96 of the metastases fromextrathoracic sites. Multiple, focal areas ofpreneoplasia or preinvasive carcinoma were present in the selected cases. The lesions ranged in severity from hyperplasia through metaplasia and dysplasia to carcinoma in situ. Aneuploid preinvasive lesions were not noted in association with the four diploid tumours but were present only when the accompanying NSCLC was aneuploid. With both central and peripheral tumours, aneuploid preneoplastic lesions were more frequent in the peripheral parts of the lung (bronchioles or alveoli) than in the central bronchi. Both the degree and incidence of aneuploidy increased with progressive severity of morphological change. Aneuploidy was not found in preinvasive lesions accompanying the Eve metastatic cases. Chu fmdingsprovidestrongsuppott fortheconceptoflieldcancerisation.
Szabo E, Riffe ME, Steinberg SM, Birrer MJ, Linnoila RI. Cancer Prevention/Control Division, Biomarkers/Prevention Res. Branch, National Cancer Institute. 9610 Medical Center Drive, RockviNe, MD 20850. Cancer Res 1996;56:305-15. Although the c-jun oncogene is an integral part of the AP-1 transcriptional complex implicated in the process of tumor promotion, its role in the pathogenesis of human tumors is unknown. We analyzed the expression and function of cJun in 110 non-small cell lung cancer (NSCLC) primary and metastatic tumors, histologically atypical areas from the surrounding lung, and 10 NSCLC cell lines to examine the role of cJun in lung carcinogen&s. cJun was expressed in primary and metaatatic lung tumors in 31% of cases, with no association with survival. Whereas normal conducting airway and alveolar epithelia in general did not express clun by immunohistochemistry, histologically atypical areas were frequently positive for cJun, regardless of the status of the corresponding tumor. Multiple members of the jun andlos gene families were frequently expressed at the mRNA level in vitro, with detectable functional activity (as defined by AP-l- specific DNA binding and/or tramactivation of an AP-l-driven reporter construct) present mall 10 NSCLC cell lines examined. Although tumor- promoting phorbol esters had little effect on c-jun expression, serum stimulation generally resulted in significant c-jun induction in NSCLC cell lines. These data show that cJun expression is altered early during human lung carcinogenesisandthatclun may hmctionasamediatorofgrowth factor signals in NSCLC.
P53 in squamous metaplasia: A marker for risk of respiratory tract carcinoma Boers JE, Ten Velde GPM, Thumiissen FBJM . Department ofPathology, University of Limburg, P.O. Box 5600, 6202 AZ Maastricht. Am J Respir Crit Care Med 1996;153:411-6. Dysplasia in squamous metaplasia of the respiratory tract was believed to be a reversible premalignant lesion. Recently, presumably irreversible genetic alterations have been demonstrated in squamous metaplasia with dysplasia in lung-resection specimens. The genetic alterations were closely similar to those in adjacent bronchial carcinoma. There remains the question of which changes in squamous metaplastic lesions are premalignant, and which of these changes predict the occurrence of carcinoma of the respiratory tract. The purpose of this study was to determine the positive predictive value for respiratory-tract malignancy of thegradeofdysplasia, p53 immunoreactivity, proliferative activity, and B&2 in bronchial biopsy specimens exhibiting squamous metaplasia. Bronchial biopsies of 51 patients with squamous metaplasia diagnosed between 1982 and 1993 were used. Immunohistochemistry was done after microwave pretreatment of the biopsy specimens. Only unequivocally stainednuclei werecounted. Normal bronchial epithelium
Extensive areas of aneuploidy are present in the respiratory epithelium of lung cancer patients
The tendency of lung cancer crude mortality rate in Ecuador. A comparative analysis with other malignant neoplasias during the decade 19844993 Freire AX, Freire NV. Servicio de Neumologia, SOLCA, Apt. Postal 09-06, 2436 Urdesa. Guayaquil. Gncologia (Ecuador) 1995;5:5-8. This study gives a global figure for Ecuador of the secular trends of lung, stomach, leukemia, cervical and breast cancer during the decade 1984-1993. Lung cancer crude mortality rate revealed an ascending trend as compared to the other malignancies that remain stable during this period. Data was obtained from the National Census and Statistics Institute (INEC) from the latest Birth and Deaths summary publication. This is the most complete mortality source available in Ecuador. The study reveals that the malignant effects of cigarette consumption are already present in our country.
Recent data on cancer due to asbestos in Germany RoslerJA,
WoitowitzHJ.
InstituteandOutpatient
Clinic, Occupational
Abstracts
/L.tatg
Cancer
I5 (19%)
139-157
be involved in lung carcinogenesis by activating carcinogens contained in tobacco smoke. Therefore, lung cancer risk should depend on both smoking exposure and CYPZD6 activity. The extent to which CYP2D6 activity, determined by using dextromethorphan, could modify the effectoftobaccowasevaluated fromastudyon 128 lung cancers and 157 controls. A strong interaction was observed; the effect of tobacco on lung cancer risk rose with increasing CYP2D6 activity (P < 0.001). Increasing levels of smoking increased lung cancer risk only among smokers with the highest CYP2D6 activity, and CYP2D6 was a risk factor only among heavy smokers. Smokers with both the highest CYP2D6 activity and daily tobacco consumption were at very high risk for lung cancer. These results may explain discrepant results of previous studies on the association between CYPZD6 activity and lung cancer.
obtained from autopsies was used as a control. In 31 patients, a synchronous or metachronous carcinoma was present (61%). Positive p53 immunoreactivity was found in 22 of the 51 patients (43 W). The positive predictive values of ~53 and of a high grade of dysplasia for carcinoma of the respiratory tract were 91% and 8096, respectively. Although the hyperproliferative state of squamous metaplastic lesions was clearly established, neither the percentage of MIB-1 labelling nor themitoticindexdistinguishedpatientgmupswithandwithoutcaminoma. No increased Bcl-2 immunostaining was found in squamous metaplasia. In conclusion, p53 immunoreactivity in squamous metaplastic lesions in bronchial biopsies is a marker of carcinoma of the respiratory tract.
Altered cJun expression: An early event in human lung carcinogenesis
Smith AL, Hung J, Walker L, Rogers TE, Vuitch F, Lee E, Gazdar AF. Simmons Cancer Center, Vniv TxSouthwestem Med CtrDallas, 5323 Harry Hines Blvd. Dallas, TX 75235-8593. Br I Cancer 1996;73:2039. According to the field cancerisation theory the entire upper aerodigestive tract has been mutagenised, thereby placing the affected individual at risk for the development of one or more cancers. To investigate this concept we studied the respiratory epithelium in lungs bearing cancer, including bronchi, bmnchioles and alveoli. After identifying preneoplastic and preinvasive lesions by light microscopy, we determined the DNA content of their nuclei in Feulgen-slained sections using a high-performance digitised image analyser. Archival material from 35 resected cases of non-small-cell lung cancer (NSCLC) was selected, including 16 central rumours (mainly squamous cell carcinomas) and 19 peripheral tumours (mainly adenocarcinomas) and five resected cases of metastatic tumour from extrathoracic primary sites. Of the NSCLCs, 3 l/35 (89 W) were aneuploid, as were 60 96 of the metastases fromextrathoracic sites. Multiple, focal areas ofpreneoplasia or preinvasive carcinoma were present in the selected cases. The lesions ranged in severity from hyperplasia through metaplasia and dysplasia to carcinoma in situ. Aneuploid preinvasive lesions were not noted in association with the four diploid tumours but were present only when the accompanying NSCLC was aneuploid. With both central and peripheral tumours, aneuploid preneoplastic lesions were more frequent in the peripheral parts of the lung (bronchioles or alveoli) than in the central bronchi. Both the degree and incidence of aneuploidy increased with progressive severity of morphological change. Aneuploidy was not found in preinvasive lesions accompanying the Eve metastatic cases. Chu fmdingsprovidestrongsuppott fortheconceptoflieldcancerisation.
Szabo E, Riffe ME, Steinberg SM, Birrer MJ, Linnoila RI. Cancer Prevention/Control Division, Biomarkers/Prevention Res. Branch, National Cancer Institute. 9610 Medical Center Drive, RockviNe, MD 20850. Cancer Res 1996;56:305-15. Although the c-jun oncogene is an integral part of the AP-1 transcriptional complex implicated in the process of tumor promotion, its role in the pathogenesis of human tumors is unknown. We analyzed the expression and function of cJun in 110 non-small cell lung cancer (NSCLC) primary and metastatic tumors, histologically atypical areas from the surrounding lung, and 10 NSCLC cell lines to examine the role of cJun in lung carcinogen&s. cJun was expressed in primary and metaatatic lung tumors in 31% of cases, with no association with survival. Whereas normal conducting airway and alveolar epithelia in general did not express clun by immunohistochemistry, histologically atypical areas were frequently positive for cJun, regardless of the status of the corresponding tumor. Multiple members of the jun andlos gene families were frequently expressed at the mRNA level in vitro, with detectable functional activity (as defined by AP-l- specific DNA binding and/or tramactivation of an AP-l-driven reporter construct) present mall 10 NSCLC cell lines examined. Although tumor- promoting phorbol esters had little effect on c-jun expression, serum stimulation generally resulted in significant c-jun induction in NSCLC cell lines. These data show that cJun expression is altered early during human lung carcinogenesisandthatclun may hmctionasamediatorofgrowth factor signals in NSCLC.
P53 in squamous metaplasia: A marker for risk of respiratory tract carcinoma Boers JE, Ten Velde GPM, Thumiissen FBJM . Department ofPathology, University of Limburg, P.O. Box 5600, 6202 AZ Maastricht. Am J Respir Crit Care Med 1996;153:411-6. Dysplasia in squamous metaplasia of the respiratory tract was believed to be a reversible premalignant lesion. Recently, presumably irreversible genetic alterations have been demonstrated in squamous metaplasia with dysplasia in lung-resection specimens. The genetic alterations were closely similar to those in adjacent bronchial carcinoma. There remains the question of which changes in squamous metaplastic lesions are premalignant, and which of these changes predict the occurrence of carcinoma of the respiratory tract. The purpose of this study was to determine the positive predictive value for respiratory-tract malignancy of thegradeofdysplasia, p53 immunoreactivity, proliferative activity, and B&2 in bronchial biopsy specimens exhibiting squamous metaplasia. Bronchial biopsies of 51 patients with squamous metaplasia diagnosed between 1982 and 1993 were used. Immunohistochemistry was done after microwave pretreatment of the biopsy specimens. Only unequivocally stainednuclei werecounted. Normal bronchial epithelium
Extensive areas of aneuploidy are present in the respiratory epithelium of lung cancer patients
The tendency of lung cancer crude mortality rate in Ecuador. A comparative analysis with other malignant neoplasias during the decade 19844993 Freire AX, Freire NV. Servicio de Neumologia, SOLCA, Apt. Postal 09-06, 2436 Urdesa. Guayaquil. Gncologia (Ecuador) 1995;5:5-8. This study gives a global figure for Ecuador of the secular trends of lung, stomach, leukemia, cervical and breast cancer during the decade 1984-1993. Lung cancer crude mortality rate revealed an ascending trend as compared to the other malignancies that remain stable during this period. Data was obtained from the National Census and Statistics Institute (INEC) from the latest Birth and Deaths summary publication. This is the most complete mortality source available in Ecuador. The study reveals that the malignant effects of cigarette consumption are already present in our country.
Recent data on cancer due to asbestos in Germany RoslerJA,
WoitowitzHJ.
InstituteandOutpatient
Clinic, Occupational