Abstracts /Lung Cancer I1 (1994) 123-150 133

epitope defined by IA10 wss expressed in all cells except one large cell carcinomacell line. However, another epitope for anti-DAF monoclonal antibody,D17,wasnotdetectedin5(71.4%)SCLCandin4(22.2%) non-small-cell lung cancer. This disparity was seen in most cell lines, irrespective of histological subtypes. The loss of D 17 reactivity seemed to be pertinent to malignant phenotype, because most of the normal pulmonary cells possessed the D17 epitope. Furthermore, a cell line lacking DAF (IAlCr/D17-) allowed alternative pathway-mediated homologous complement (C3) deposition after pretreatment with anti- MCP antibody. This raises P new possibility for immunotargeting of cancer. These cell lines should be useful in studying the biology of lung cancer.

Pathology

Y chromosome loss and rearrangement in non-small-cell lung cancer CenterR, LukeisR, V-V, GarsonOM.DeparrmenrofCyrogenerrics, St. Vincent’s Hospital. Fitzroy, Vie. 3065. Int J Cancer 1993;55:390- 3.

While loss of the Y chromosome from the karyotype of tumor cells has frequently been found in a number of human malignancies of different types, structural alterations are a much less common tinding. Prompted by the high frequency of cytogenetic Y chromosome loss found in primary non-small-cell lung cancer (NSCLC), and the fact that NSCLCkaryotypesusuallycontain markerchromosomesofunidentified origin, we have determined the Y chromosome status of 12 NSCLC samples (7 cell lines and 5 primary tumors) at a molecular level. Of the 9 cases which did not have a cytogenetically detectable Y chromsome, 4 were negative for all the Y sequences tested. The other 5, in contrast, retained some Y chromosome sequences. In 1 case (H520), only Yq heterochromatic sequences were detected, whereas in the remaining 4 (L162, L93, L125 and Wl) both Yq heterochmmatic sequences and Y euchromatic sequences were retained. The region of common overlap for loss of Y euchromatin was Yp distal to the Y centromere. We hypothesize that deletion of Yp sequences may play a role in tumor progression in NSCLC due to loss of a tumor-suppressor gene.

Immunohistochemical analysis of cathepsin B expression in human lung adenocarcinoma: The role in cancer progression Ozeki Y, Talcishima K, Tskagi K, Aida S, Tamai S, Mamiya G et al. Department of Biochemistry. NationalDefense Medical CoUege. Nomiki 3-2, Tokorozawa, Saitama 359. Jpn J Cancer Res 1993;84:972-5.

Production of cathepsin B by tumor cells has been linked to metastatic potential in several experimental models. Sections of 95 priIllalylungadewcarcinomaswereexaminedforexpressionofcathepsin B using a standard avidin-biotin immunohistochemical technique. Staining for cathepsin B was observed in 22.1% of all cases and 28.0% of those of the Clam cell type. In Clam cell adenocarcinomas, cathepsin B expression correlated with positive lymph node status, presence of distant metastases, and poor prognosis (P < 0.05). However, no correlation with clinical outcome was observed in other cell types. Our data suggest that cathepsin B may be involved in invasion and metastasis in Clara cell lung adenocarcinoma.

Charncterisation of human tumour cell lines using antibodies to intermediate filaments Moorthi C, Willers I, Ressler B, Goedde HW. Inrritute of Human Genetics, Universiry of Hamburg. Butenfeld 32, D-22529 Hamburg. Pathobiology 1993;61: 197-9.

The human hepatoma cell line G2 (Hep G2) has been compared to lung carcinoma, sarcoma and skin fibroblasts for the expression of intermediate filaments, i.e. vi-tin and cytokeratin. The immuno- fluorescence study revealed that cytokemtin and vimentin are absent in Hep G2. Human skin fibroblasts and sarcoma cells expressed vimentin as expected for their mesenchymal origin, but a positive reaction to vimentin could also be shown in lung carcinoma cells. However, the vimentin filament structure of both these tumour cell lines was different in comparison with skin fibroblasts. Therefore determining the exact tissue origin of tumour cell lines by means of intermediate filament characterization remains doubtful.

Clinical assessment

Two bombesin analogues discriminate between neuromedin B- and bombesin-induced calcium flux in a lung cancer cell line Ryan RR, Daniel JL, Cowan A. Department of Pharmacology, Temple University, School of Medicine, Philadelphia, PA 19140. Peptides 1993;14:1231-5.

We examined the profile of two bombesin (BN) antagonists (CH,)*CHCO-His-Trp-Ala-Val-D-Ala-His-Leu-NHCH,] (ICI 216140) and [D-Phe6,des-Met”]BN(6-14)ethylamide (DPDM-BN EA), against neuromedin B-induced Ca** mobilization in the small cell lung cancer (SCLC) line NCI-H345. Neuromedin B (NMB), a BN-like peptide sharing sequence homology with ranatensin, elicited a concentration- dependent C& release (in part) from intracellular stores. Sequential addition of NMB attenuated G?’ mobilization. Desensitization occurred between BN and NMB; depletion of intracellular Ca*’ is a likely mechanismbecausethapsigarginstimulatedCa*’releasea~eramaximaUy desensitizingdoseofNMBICI21614OandDPDM-BNEAcompe~itively inhibited BN-induced Ca” transients. In contrast, these compounds antagonized NMB-stimulated Ca2’ transients in anoncompetitivemanner. The pharmacological profiles obtained support receptor heterogeneity for BN-like peptides on this SCLC line, underscoring the need for thorough examination ofdose response relationships when investigating effects of BN analogues on intact cells.

Early squamous lung cancer and longer survival rates I&da T, Inoue T, Sugio K, Inoue K. Inuxuka S, Tateishi M et al. Department of Surgery II, Fact&y of Medicine, Kyushu University. 3- 1-1 Maiainhi, Higashi-ku. Fukuoka 812. Respiration1993;60:359-65.

The criteria for early squamous lung cancer rempin open to discussion as patients who have been treated for early stage lung cancer, such as TINOMO, and appear to have been cured clinically may die from recurrent or me&static tumors. We reviewed the pathological data on 242 surgical patients with squamous lung cancer and found 31 cases (13 W) of early lung cancer, included were early lung cancer of the hilar type as a lesion restricted to the bronchial wall without lymph node involvement, and early lung cancer of the peripheral type as a lesion of less than 2 cm and surrounded by visceral pleura but without lymph node involvement. Of 89 patients with hilar-type squamous lung cancer, 17 (19%) had early lung csncer, and 14 (9%) of 153 patients with peripheral-type squamous lung cancer had early lung cancer (p < 0.05). For early lung cancer of the hilar type, all but 1 (94 96) were detected using sputum cytologic study and bronchoscopy. For early lung cancer of the peripheral type, all were detected on chest X-ray, but 57 96 were cytologically proven to be malignant. The 5-year survival rate for patients with early lung cancer, according to this new criteria is 90%; 92% for the hilar type and 88% for the peripheral type. Thus,

134 Abstracts/Lung Cancer II (1994) 123-150

classification of early squamous lung cancer is pertinent for determioing the prognosis and selection of treatment. We emphasize that efforts be made to detect early lung cancer.

Chromosome abnormalities in non-small cell lung cancer pleural effusion% Cytogenetic indicators of disease subgroup Lukeis R, Ball D, Irving L, Garsoo OM, Hasthorpe S. Cell Biology, Peter MacCallum Cancer Institute, Melbourne, Vie. 3lXX7. Genes Chromosomes Cancer 1993;8:262-9.

A cytogenetic study of pleural eftitsions (PE) containing metastatic or invasive tumor cells from 11 patients with non-small cell lung cancer (NSCLC) (3 squamous cell carcinomas [SQC] and 8 adeo-inomas [ADC] including 1 giant cell variant) was performed to identify non- random chromosome abnormalities Numerical abnormalities seen in 30% of cases included gain of chromosomes 7 and 20, and loss of chromosomes4,9,10,13,15,16,18,19,21,and22.Tltemostfrequeot structural abnormality involved rearrangement in lp with breakpoints clustering at lplO-~13. other recurrent breakpoint regions, seen in 30% of cases, occurred in chromosome regions 3plO-p21,3qllq25, 6pll-~25, 6q13q23, 7qllq36, 9q32q34, llpll-~13, llq13- q24, 13~114~ and/or Hip, 17p and 19p, with, in particular, apparent loss of 6q21-q27,3p21-p26,7q2lq22,9p22-p24(shorteatregionsofcommon overlap)and 17~. Therewasalsorectnreotgainof lq23q44,8q13q24, and 1 lq13q23. These abnormalities were not restricted to a particular histological subtype, with the exception of + 8 and a breakpoint in 9q32- q34, which were seen only in ADC. The 9q32q34 breakpoint observed in 4 ADC PE (including 1 giant cell variant) represents a new observation in NSCLC. These findings, when compared to those reported for primary NSCLC indicate cytogeoetic differences between the two which may be associated with pleural invasion of NSCLC.

Satellite PET and lung cancer: A prospective study in surgical patients Slosman DO, Spiliopoulos A, Couson F, Nicod L, Louis 0, Lemoine Ret al. Division ofNuclearMedicine, University Hospital, 1211 Geneve 14. Nucl Med Commun 1993;14:95561.

Positron emission tomogmphy (PET) appears to be an innovative method for imaging the proliferative activity of malignant tissue, iu particular by means of ‘*F-labelled fluorodeoxyglucose (FDG). The potential role of PET scanning was investigated in a satellite ceotre as an adjunct to cooventiooal methods for estimating the likelihood of pulmonary malignancy. Therefore the sensitivity of detection of lung cancer in candidates was determined prior to exploratory or therapeutic thoracotomy by FDG PET imaging. Thestudy involved 36 patients with abnormal chest roeotgeoogram and suspected lung cancer who were due for thoracotomy. The PET scans were evaluated qualitatively and semiquantitatively. Pulmonary malignancy was found in 31136 patients and 29 had a focal increase in FDG pulmonary uptake. Benign pulmonary lesions were found in 5/36 patients, three of whom had a negative PET scan. The sensitivity of detection of lung cancer by FDG PET was therefore 93.5 I. Bayesian study shows that FDG PET could be the most useful method in a population with a low prevalence of lung cancer. As illustrated by our study, a simple FDG PET scanning protocol in a satellite PET centra could provide adequate clinical information and help in deciding subsequent patient management.

Immune response induced in small-cell lung cancer by maintenance therapy with interferon gamma Pujol J-L, Giboey DJ, Su JQ, Maksymiuk AW, Jett JR. Division of Medical Oncology, Mayo Clinic, 200 First St., SW, Rochester, MN 55905. J Nat1 Cancer Inst 1993;85: 1844-50.

Backgroundz Chemotherapy, with or without radiotherapy, results

ina30%-40% completerespooserateinsmpll-celllungcancer(SCLC), but approximately 90% of patients who have complete remission die within 2 years after relapse with chemoresistant disease. Randomized clinical studies of maintenance chemotherapy aBer complete response have failed to demonstrate survival advantage. However, studies have shown that the human cytokine interferon gamma (IFN-gamma) induces immune response in humans, including T-cell activation and expression of class II major histocompatibility complex (HLA- DR) and receptor for the Fc portion of immunoglobulin on mooocytes. It has also been demonstrated that recombinant IFN-gamma (rIFN-gamma) induces immuoomodulatioo and has anti-proliferative activity. Purpose: In vivo effects of rIFN-gamma treatment were characterixed by flow cytometric analysis of peripheral blood mononuclear cells in patieots with SCLC who received rIFN-gamma as maintenance treatment. Methoak After induction chemotherapy and radiotherapy, 100 patients who achieved a complete remission were randomly assigned to receive rIFN-gamma at a dose of 0.2 mg (4 x lo6 units) once a day, subcutaneously, for 6 months, or observation only. Jn 31 patients, peripheral mononuclear cells were obtained prior to tbe study and at weeks 4,8, and 12 for serial monitoring of immune response. By flow cytometric analysis, we ideotifiedthelymphocyteandmooocytepopulationsusiogcharacteristic differences in electronic volume and right-angle scatter. IO these populations, we determined the mean fluoreacencechannel after staining for CD14 (antigen expressed oo mooocytea), CD3 (antigen expressed on T lymphocytes), and HLA-DR (HLA class II expressed by mooocytes and activated lymphocytes). To determine the number of Fc receptors per cell, an Fc receptor assay was performed using the mooocyte cell line U937 as a standard. Results: At weeks 4,8, and 12, expression of HLA- DR and Fc receptors on mooocytes in patients who received rIFN- gamma was significantly higher than that in untreated patieots, and the difference was statistically significant. The number of Fc receptors per mooocyte consistently increased during the rIFN- gamma treatment and reached a fivefold elevation at week 12. There was oo statistically significant difference in lymphocyte surfaceantigen expressionbetween the treated and untreated groups. Conclusion: The dose of rIFN-gamma used in this study resulted in immune stimulation in patients with SCLC who had complete remission after induction therapy. The in vivo inununomodulatory activity of rIFN-gamma in such patients is characterized by a strong mooocyte activation but no significant alteration in T-cell activation.

Bronchogenic cancer in patients under 40 years old: The experience of a Latin American country Greea LS, Fortoul TI, Poociano G, Robles C, Riven, 0. Chest 1993;- 104:1477-81.

Lung cancer in young patients is increasing in frequency, as documented by data from the United Statea, Canada, Japan, and European countries. However, to date and to our knowledge, there have not been any reports from Latin America on this topic. The published reports show that lung cancer in young patients is associated with smoking habit and family history of lung cancer. Its clinical course seems to be more aggressive than in older patients and the histologic type is less o&n squamous type. We describe 48 patients, aged 40 years or younger, who were diagnosed as having lung cancer in the Jnstituto National de Cancerologia from 1980 to 1990. The patients were equally divided between meo and women. Smoking was documented for only 46 percent of the cases. The histologic type most frequently diagnosed was adeoocarcinoma (N = 26) followed by squamous cell carcinoma (N = 12). Almost all the - (46 casea) were staged IV according to the TNM classification. A group of 33 patients older than 40 years (56 to 82 years) were used for comparison. The differences in sex ratio that were higher for men in the elder (m/f, 2.7: 1) were family history for cancer in six patients elder; positive smoking habit in all the aged