Abstracts/ Lung Caneer I2 (1995) 113-160 127

Detection of resistance proteins in matched primary lung tumors and lymph node metastases Mattern J, Volm M. Dept @II, German Cancer Reseamh Centec Im NeuenheimerFeld280,69120 Heidelberg. AnticancerRes 1994;14:417- 9. The expression of several resistance markers (P-glycoprotein, glutathione S-transferased, tbymidylate syntlmm, dihydrofolate reductase) was analyzed in matched primary tumors and lymph node memstases from 2 1 patients with lung cancer using immunohistochemistry. The analysis showed that expression of these maistance proteins is generally congruent in primary lung cancer and simultaneously resected lymph node metastases. This suggests tbat in general the resistance of a primary tumor predicts for the resistance of the metastases and vice versa.

Karyotypic characterization of broocbial large cell carcinomas Johansson M, Dietrich C, Mandahl N, Hambraeus G, Johansson L, Clausen PP et al. Depwtment of Clinical Genetics, Univers@ Hospital, S-22185 Lund. Int J Cancer 1994;57:463-7. Qtogenetic analysis of short-term cultures from 26 primary bronchial large cell carcinomas and 1 metastasis from a primary large cell carcinoma revealed clonal chromosome abnormalities in 20 tumors and a normal kaiyotype in 6. No outgrowth was obtained in 1 case. Simple aberrations were present in 3 tmnors; in 1, the only change was a reciprocal translocation between chromosomes 1 and 6, in another the sole anomaly was a supernumerary marker ring chromosome and in a third loss of the Y chromosome was the only clonal change. The remaining 17 tumors had complex karyotypes. The chromosomes most frequently involved in structural rearrangements were chromosomes 1, 2,3,5,6,7,8,10,11,13,14 and 17. The bands most frequently affected were lqll-12, lp13,7qll, and 17~11-13. The rearrangements led to repeated losses of 1 p, 1 q, 3p, 6q, 7q and 17p and gains of 5q and 7p. The emerging karyotypic picture oflarge cell lung carcinomas indicates more similarities with adenocarcinomas than with other pathologic subgroups of lung cancer.

Genesis of squamous cell lung carcinoma: Sequential chaoges of proliferation, DNA ploidy, and pS3 expression Hirano T, Franzen B, Kato H, Ebihara Y, Auer G. Division ofTumor Pathology, Department ofPathology, Kamlinska Hospital andinstitute, I71 76 Stockholm. Am J Path01 1994; 144:296-302. Squamous cell lung carcinomas (SCCs) represent a highly malignant group of tumors, and effective treatment is greatly dependent upon early diagnosis. However, objective diagnosis of atypia is diflicult and useful markers need to be defined. In this study, genomic instability, cell proliferation, and cellular accumulation of mutant ~53, as reflected by DNA aneuploidy, proliferating cell nuclear antigen, and ~53 immunoreactivity, respectively, were. evaluated in bronchial squamous metaplasia without atypia (n = 4), bronchial squamous metaplasia with low-grade atypia (n = 12), bronchial squamous metaplasia with high- grade atypia (n = IS), early-stage SCC (n = IS), and advanced-stage SCC (n = 33). Our results suggest that hypetproliferation is an early event followed by DNA aneuploidy, which in turn precedes ~53 immunoreactivity in the genesis of SCC. We conclude that routine assessment of proliferating cell nuclear antigen, DNA ploidy, and ~53 may be valuable for the early diagnosis of SCC.

Establishment of anti-idiotype monoclonal antibodies (Ab26) for specific and active immunotherapy in lung cancer patients Fnkasawa T, Yamaguchi Y, Saito H. Department of Su@ery. Institute of Pulmonary Cancer Res., Chiba University &hool o/Medicine, Chiba- shi. Lung Cancer (Japan) 1994;34:143-51.

For specific and active immunotherapy in lung cancer patients, we established four anti-idiotype antibodies (Ab28) to human monoclonal antibody 4G12 (IgM, lambda) which reacts strongly with squamous cell lung carcinomas and other malignant tumors. Murine splenocytes immunized with 4G12 monoclonal antibody were fused with mouse myeloma cells (p3Ul) to establish anti-idiotype monoclonal antibodies. After repeated screening and cloning, we established four clones secreting IgG, kappa monoclonal antibodies which specifically react with 4G12 antibody, but not with human IgM, IgG or serum. Inhibition assay showed that all of these antibodies inhibited about 90% of the binding reaction between ‘*‘I-labelled 4G12 antibody and human squamous cell lung cancer cells (PClO). From these data, they were recognized to be Ab26 antibodies Furthermore, cross-inhibition tests between each Ab26 antibody revealed that four Ab28 antibodies are recognized to reacting with at least three idiotopes of 4G 12 antibody. When mice well immunized with each Ab26 antibody, anti-serum (Abs serum) was produced, and two of four Ab3 sera reacted with PC10 cells. In conclusion, two Ab28 antibodies have internal image against 4G12 antibody, and might be useful for specific and active immunotherapy in lung cancer patients.

Expression of the multidrug resistawe gene (MDRl) in non-small cell lung cancer Abe Y, Nakamura LM, Ota E, Gzeki Y, Tamai S, Inoue H et al. Department of Pathology, Tokai University School of Medicine, Bohseidai, Isehara-shi, Kanagawa 259-11. Jpn J Cancer Res 1994;85:536- 41. To examine the clinical relevance of P-glycoprotein, encoded by the human multidrug resistance gene (MDRl), to multidrug resistant in lung cancer, we examined the expression of MDRl in 107 non-small cell lung cancer (NSCLC) specimens and 20 corresponding specimens of normal lung tissues. We also evaluated the relationship between MDRl expression and the histopathology and pathological staging of NSCLC. The tumors consisted of 60 adenocarcinomas, 38 squamous cell carcinomas, 8 large cell carcinomas, and 1 adenosquamous carcinoma. MDRI expression was semiquantifled by use of the reverse tmnscriptase-polymerase chain reaction method. We sub classitied the NSCLC into 3 grades according to the MDRl expression level (-, +, ++). Sixty-one of the 107 tumor specimens (57%) and 18 of the normal lung tissue specimens (90%) expressed various levels of the MDRl gene. Only one tumor specimen showed higher MDRI expression than the corresponding normal lung tissue. The relationship between p8thologic8l stage and MDRl expression levels was not significant. These results suggest that the level of MDRl expression in lung cells is decreased as cells progress from the normal to the transformed state.

A study of thymidioe kinase activity in lung cancer tissue Yusa T, Tamiya N, Yamaguchi Y, Takeda T, Ogawa T, Kimura H, Fujimura S. Department of Surgery, Chiba Rosai Hospital, Chiba-shi. Jpn J Thorac Dis 1994; 32:211-5. In order to investigate the usefulness of thymidine kinase, which acts to salvage tbymidine to its nucleotide for DNA biosynthesis, as a marker of malignant in lung cancer, the enzyme activities in extracts of tumors and uninvolved lungs of 83 resected cases of lung cancer were determined. The mean value of thymidine kinase activity in tumors was as much as 4.3 times higher than that of uninvolved lungs. There was no significant correlation between the activity in tumors and clinlcopathological findings such as histological type, the grade of histological diRerentiation, pT thctor, pN faaor, pTNM stage and tumor size. The tumor doubling time did, however, show a sign&ant inverse