Abstracts/Lung Cancer I5 (19%) 139-157 145

denaturated (d) forms of this antigen. The present study further characterized the differences in the epitope profiles recognized on BLG. Methods. The capacity of individual sera from 65 lung cancer patients, tested before and after cancer removal for the patients with early stage lung carcinoma, 65 healthy controls, and 52 patients with COPD, to prevent the binding of pooled IgG fractions from each population as well as muriae monoclonal antibodies (MoAb), specific for BLG, to solid phase bound antigen was evaluated in enzyme-linked immunoadsorbent assay using streptavidin biotin technology. Some of these experiments were also performed with sera from 42 patients diagnosed with other cancers. Resulrs. Compared with control sera and sera from patients with other solid tumors, lung cancer patient sera showed distinct capacities to prevent the binding of murine MoAb as well as human pooled IgG fractions lo n- and d- BLG. The inhibition capacities of lung cancer sera changed as soon as five weeks after cancer removal. Conclusions. Tberesultsindicatethat thedifferenceinepitopespecificity exhibited by lung cancer sera is not restricted to cryptic epitopes, but also affects continuous and discontinuous epitopea, accessible only on the native antigen. A high level of binding discrimination between antibodies From the study populations is also observed at the level of the epitopa. This deviation in the epitope specificity of antibodies changes soon after cancer removal, suggesting a tumor-dependent disturbance. Also documented in the Dermatophagoides pteronyssinus model, it opens the way to a new class of paraneoplastic immune markers for this malignancy, with, at first glance, a high specificity level.

Frequent loss of heterozygosity in region of the KIPl locus in non-small cell lung cancer: Evidence for a new tumor suppressor gene on the short arm of chromosome 12 Takeuchi S, Mori N, Koike M, Slater J, Park S, Miller CW et al. Cedars-Sinai Medical Center, UCLA School of Medicine, 87GfJ Beverly Boulevard, Los Angeles. CA 90048. Cancer Rea 1996;56:738-40.

Torefinethechromosomal localizationofaputativetumorsuppressor gene, we analyzed the loss of heterozygosity (LOH) of chromosome 12 in 36 primary non-small cell lung cancer (NSCLC) samples with matched normal DNA using 22 highly informative polymorphic markers. Twelve cases showed LOH at one or more loci on chromosome 12. LOH of chromosome arm l2p was more frequent in large cell carcinoma than squamous cell carcinoma, indicating molecular genetic heterozygosity within the major NSCLC subtypes. We identified the smallest commonly deleted region on chromosome 12~13. This region is flanked by D12S269 and D12S308, including the KIPl gene. Mutational analysis of KIPl using PCR-single strand conformation polymorphism and Southern Blot analysis showed no homozygousdeletions, rearrangements, or point mutations, suggesting that the altered gene in this region is not the KIPl gene. These data suggest that a new tumor suppressor gene which is involved in rumorigenesis of NSCLC is in the region of KIPl.

Expression of IGF-I, TGF-a and ~53 protein in imprint smears of bronchial biopsy specimens of lung cancer Orphanidou D, Athanasiadou P, Toumbis M, Rasidakis A, Petrakakou E, Dimakou K et al. Departmen; of Respiratory Medicine. Medical School University, Chest Diseases Hospital, 152 Mesogion Ave., Athens II5 27. Oncol Rep 1996;3:75-80.)

The expression of insulin-likegrowth factor-1 (IGF-I), transforming growth factora (TGFa) and ~53 protein was examined in bronchial biopsy imprint smears of patients with primary lung cancer and benign lung disorders, by immunohistochemistry. Of the 44 malignant imprint smears, 26 (59 96) were positively stained for IGF-I, I8 (41%) for TGF- a and 29 (66%) for ~53 protein. In contrast, of the 36 benign imprint smears none was positively stained for IGF-I (p < 0.001). whereas 7

were positively stained for TGF-a (p > 0.05) and 3 for ~53 protein (p < 0.001). There was no correlation between the expression of the examined markers and the histological type of lung cancer. The most sensitive indicator of malignancy was ~53 overexpression (65.9 %), the mostspecificwasIGF-I(lOO%) whereasbothrevealed77.596 accuracy. The combination of IGF-I and ~53 revealed 75% sensitivity, 91.6 96 specificity and 82.5% accuracy. When one marker was positive the relativepossihilityoflungcancerwas67.146. T&possibility increased to 77.7 % when two markers were positive and to 100% when three markers were positive. These results suggest that the evaluation of IGF- I and ~53 in imprint smears could be of value in diagnosis of lung cancer.

Pathology

Histologicchangesinsmallcell hmgcarcinomaafter treatment Fushimi H, Kikui M, Merino H, Ya-oto S, Tateishi R, Wada A et al. Department of Pathology, Osaka Prefectoral General Hospital, 3- 1-56 Mandai Higashi. Sumiyoshi-ku, Osaka 558. Cancer 1996;77:278- 83.

Background. Small cell lung carcinoma (SCLC) has been divided into three subtypes; pure SCLC, mixed small cell/large cell carcinoma (mixedSC/LC), andcombinedSCLC. Patientswithmixed SClLCshow a worse prognosis than those with pure SCLC. Methods. Persistence of histologic subtype in SCLC in the primary sites during the course of treatment or in the different organs at autopsy was examined. For this purpose, biopsy or cytologic specimens before chemotherapy, and autopsy specimens from I75 patients with SCLC were reviewed. They included 117 (84 96) men and 28 (I6 W) women with an age range of 29- 83 (median, 65) years. Results. The frequency of mixed SClLC in the primary sites was statistically higher in autopsy (14.3%) than that in biopsy or cytology specimens (8.6 %) (P < 0.05). At autopsy, involved organs were categorized into two groups according to frequency of appearance of mixed SC/LC i.e., a higher frequency group, including Iheliver931of85;36.4%),adrenalgland(I5of56;26.8%),brain16 of 9: 66.7 %), and extratboracic lymph nodes (17 of 59; 28.8 96) and a lower frequency group, including the lung (metastatic sites) ( 12 of 102); 11.8%). pleura (B of 74; lO.S%), and intrathoracic lymph nodes (12 of 94; 12.8 96). The difference in frequency between these two groups was statistically significant (P < 0.05). Conclusions. These findings suggest that primary pure SCLC can progress to mixed SClLC with an increased potential for distant metastasis.

Immunohistochemical analysis of ~53 mutations in bronchioalveolar carcinoma and conventional pulmonary adenocarcinoma Wang X, Samhasiva Rao M, Yeldandi AV. Department of Pathology, Northwestern Universiry Medical Sch., 303 Easy Chicago Avenue, Chicago, XL 65611. Mod Pathol 1995;8:919-23.

Mutations of ~53 tumor suppressor gene have been shown to contribute to tumorigenesis in a variety of human cancers. Normally, ~53 protein degrades rapidly and is not detected by immunohistochemical procedure, but mutant ~53 and wild-type ~53 stabilized by certain viral oncoproteins can accumulate to immunohistochemically demonstrable levels. Conventional pulmonary adenocarcinomasand bronchioalveolar carcinomas,altbough morphologically similar, exhibitdifferentbiological behavior and clinical prognosis. To explore the differences in the expression of ~53 protein in these two tumor types, we performed immunohistochemistryon 10conventionalpulmonaryadenocarcinomas and 12 bronchioalveolar carcinomas on formalin-fixed and paraffin- embedded material, using the commercially available monoclonal