430 Abstracts /Lung Cancer I I (1994) 423-444

Cancer Research Division, Depamnent of Otokzryngology. Johns Hopkins Univ. Sch. of Medicine. 720 Rutland Avenue, Baltimore, MD 21205-2195. Cancer Res 1994;54: 1634-T.

The Johns Hopkins Lung Project developed an archive of sputum specimens during a randomized trial of lung cancer screening (1974- 1982). We identified 15 patients from that trial who later developed adenocnrcinoma of the lung. Tbe primary lung carcinomas from 10 of these 15 patients contained either II ras or a ~53 gene mutation. Using apolymerasechainreactioo-basedassay, storcdsputumsamplesobtained prior to clinical diagnosis were examined for the presence of these same oncogenemutations. 10 8of 10 patients, the identical mutation identified in the primary tumor was also detected in at least one sputum sample. The earliest detection of a clooal population of cancer cells in sputum was in a sample obtained more than 1 year prior to clinical diagnosis. These results provide the basis of a novel approach for detection of lung cancer based on the evolving molecular genetics of this disease.

Receptor subtype expression and res~nsivewss to bombesin in cultured human bmncbii epithelial cells Frankel A, Tsao M-S, Viallet J. Montreal General Hospital, 1650 C&r Avenue, Montreal, Que. H3G IA4. Cancer Rea 1994;54:1613- 6.

We detected low level expression of the gastrin-releasing peptide and oeuromedin-Brec+tormRNAsincultun+sofhumanbmnchiale.pitbelium from 4 of 6 individuals. Bombesin receptor subtype-3 mRNA was undetectable in these cells. An elevation of intracellular calcium concentration was observed in response to bradykinin (6 of 6) and neurotensin (1 of 5) but not to bombesin (0 of a), vasopressin (0 of 6), or cholecystokinin (0 of 3). In contrast, such mapo- are frequently noted in lung cancer cell lines. Bombeam did not stimulate the in vitro growth of an immortalized human bronchial epithelium cell line expressing low levels of bombesin receptor mRNAs. We conclude that bomb&o receptors are expressed at low levels in human bronchial epithelium cells which may acquire greater responsiveness to multiple oeuropeptidea in the course of multistep carcinogenesis.

Detailed deletion mapping of the short arm of chromosome 3 in anall cell and non-small cell carcinoma of the lung Hosoe S, Shigedo Y, Ueno K, Tachibana I, Gsaki T, Tanio Y et al. Department of Medicine III, Osaka Uniwrsity Medical School, 2-2. Yamadaoka. Suita, Osaka 565. Lung Cancer (Maod) 1994;10:297- 305.

We~mc~adetadeddeletioomapoftheshortarmofchromosome 3 (3~) for 55 lung cancer c1se8 by using 17 restriction fragment length polymorphism(RFLP)probes. Initially, we examined40small cell lung cancer (SCLC) cases and found three regions of deletion at 3~25-26, 3~21.3 and 3pl4-cen, suggestingthepossibility ofat lesstthreedifferent tumor-suppressor genes on 3p. IO order to obtain more detailed deletion area, and to compare the pattern of 3p deletion, we also examined 15 non-small cell lung cancer (NSCLC) cases. Compared to NSCLC cases, most of SCLC casea have widespread deletion on 3p, suggesting multiple tumor-suppressor genes on 3p may be inactivated in this type of cancer. IO 3~21.3 area, minimum overlapping area of deletion lays between two probes which are close to each other. These. data will be useful to isolate the putative tumor-suppressor genes located on the chromosome 3p.

Immunohistocbemical demonstration of glycopmtein 170 and glutathione S-transferase isoenzymes in normal and neoplaatic bronchial tissue Wossner R, Toomea H, Fritz P, Lioder A, Dierkesmann RE, Behrle E

et al. Pathologic. Robert Bosch Krankenhaus, Auerbachstrasse 1 IO, D- 70376 Stuttgart. Gnkologie 1994; 17~28-34.

Background: The aim of this study was to demonstrate the content ofdrug-transportingand-metaboliz.ingeozymeainprimarylungcancer. Material and Metho& We investigated 20 specimens of lobectomies, bilobectomiea, pneumooectomies and extended pneumooectomies of patients suffering from lung cancer. Results: IO normal broochial tissue and various primary lung tumors, we observed a high content of glycoproteio 170 (gp 170), and glutathiooe S-transferase (GST) placenta (a) and liver (a) typea. Gp 170 and GST a were localized in columnar epithelium, excretory ducts, serous glands, muscles, cartilage, nerves and vessel walls. Nine of 12 squamous cell carcinomas showed a considerable quantity of gp 170, comparable with the amount of gp 170 in the proximal tubules of the kidney. All of them stained for GST a. GST a was demonstrable to a lesser extent than GST a. only few of the carcinomas stained markedly positive for GST a. There was no cor- relation between the quantity in normal bronchial tissue and the corresponding tumor for any enzyme studied. Conclusions: If gp 170 and GST play a role in primary chemoresistance, especially in multiple drug resistance, our results explain the high rate of primary chemo- resistance in non-small cell lung tumors.

Tumor epidemud gmwth factor receptor studies in patients with non- anall-cell lung cancer or head and neck cancer treated with monoclonal antibody RG 83852 Perez-Soler R, Dooato DJ, Shin DM, Roseoblum MG, Zhang H-Z, Tornos C et al. l%omcic/Head/NeckMed. On& Dept., M.D. Anderson Cancer Center, Box SO, 1515 Holcombe Blvd. Houston, Ix 77030. J Clin Gncol 1994; 12730-9.

~:Tumortyrosinekinaseactivityassociatedwithtbeepidermal growthfactorreceptor(EGFR)PndlocaliEatiooofaoti-EGFRmonoclonal antibody RG 83852 were studied in patients with non-small-cell lung cancer (NSCLC) and head and neck cancer. Patients and Methods: Fifteen patients were treated with escalating doses of RG 83852 by continuous intravenous infusion for 5 days. Fresh tumor specimens were obtained 24 hours after therapy in 10 patients (of whom five had a pretherapy sample taken). Tumor EGFR tyrosine kinase activity was determined in fresh tumor samples by autopbosphorylatioo of EGFR isolated in immuoocomplexes with RG 83852. Tumor EGFR saturation with RG 83852 was assessed semiquantitatively by comparing the EGFR tyrosinekinaseactivityinimmuoocomplexesoftumorspecimens obtained after therapy with total EGFR tyrosioe kinase activity assessed by exogenous addition of RG 83852 to tumor lysatea. Modulation of EGFR tyrosioe kmase activity after the administration of RG 83852 wss assessed by comparing EGFR tyrosine kmaae activity from the same malignant lesion obtained before and after therapy. Tumor localization of RG 83852 and EGFR saturation were also assessed by immuno- hi&chemistry. Results: No significant side effects were observed up to a total dose of 600 mg/m’. Based on tyrosioe kioase activity, a high degree of EGFR saturation ( 50%) was observed at doses 200 mglm’, and EGFR saturation was estimated to be 100% at a dose level of 600 mglm’ both in tumor tissue and skin used as surrogate EGFR-positive tissue. Immunohistochemistry studies showed that RG 83852 localized intumortissueandskin, butootinstmma, atdoses 4OOmglm’, andhigh EGFR saturation was observed at 600 mg/m*. Tumor EGFR tymsine kinase activity was studied in five patients (four with EGFR-positive tumors) before and 24 hours posttherapy; a threefold to fourfold upregulation of EGFR tyrosinekinase activity in posttherapy specimens was observed in two patients. Moderate upregulation of EGFR itself was suggested in both of these patients and in two additional patients by immunohistochemistry. Conclusion: RG 83852 causea no toxic effects at doses that result in high tumor EGFR saturation. Treatment with RG 83852 may enhance EGFR tyrosine kioase activity and/or EGFR expression. BecausehighEGFRexpressionbytumorshasbearassociated