Intermediate filament expression in small cell lung cancer

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exploration. To define the metastases to which lymph nodes exclude curative resection requires further studies. Prognostic Value of Flow Cytometrically Determined DNA Content in Surgically Treated Lun~ Cancer Patients. 2 Modini I C., Tirind~lli Danesi , ~., Cicconetti-,1F., Botti , C., Teodori , L. 1 1 Aschelter , A.M., Buttini , G.L., Stipa , S. i. ist Department of Surgery-University of Rome. 2. ENEA-Casaccina, Rome, Italy. 290 tumor samples from 91 pts with histologically proven lung cancer were analyzed by flow cytometry to find out a relationship between cellular DNA content expressed by DNA index (D.I.) and recognized prognostic determinants such as stage of disease, cell type and doubling time (D.T.) of the primary tumor when available (43 cases). Aneuploidy was present in 89/91 cases (98.7%) and multiclonality in 50/91 (54.9%). Nevertheless multiclonality rate was 64.7% (44/68) when assessed by multiple surgical specimens of the primary tumor (core and periphery) vs. 26.1% (6/23) in the other cases (bronchial washings, biopsies or needle aspirates) (p < 0.005); this difference depends on the inadequacy of the non-surgical sampling; thus we excluded those 23 pts from the following comparisons. We divided the remaining 68 cases in 2 groups: A=D.I. 2.00; B=D.I.> 1.00 and < 2.00. No differences were found between these groups in terms of TNM staging and cell type distributions. 4/19 cases (21%) of the group A were slow growing tumors (D.T. > 90 days) vs 8/15 (53.5%) in the group B (p < 0.05). A minimum follow-up of 12 months (according to the observed overall median survival) was achieved for 60 out of 68 pts. The 12 mths survival rate in group A and B were respectively 52.9% (18/34) and 86.4% (19/22) (p < 0.05), 4 operative mortalities being excluded. Such survival differences between group A and B were statistically significant even after TNM stratification (p < 0.05). The worst and the best prognoses were respectively observed in group A-fast growing tumors and in group B-slow growing one (p < 0.001). Both D.T. and D.I. are able to differentiate the prognosis of patients within the same stage and same surgical treatment group. Role of the T~nor Volume and Doubling Time in Lung Cancer: Prognostic and Therapeutic Implications. i Modini , C., De MeesSer, T, Cicconetti , 1 F., Tirindelli Danesi , D, ~asquali Lasag~i , R., Albertucci, M., Buttini , G.L., Stipa , S. I. Ist Department of Surgery-University

of Rome. 2. Enea-Casaccia, Rome, Department of Surgery University of Omaha. On 114 histologically proven bronchopulmonary carcinomas the primar tumor volume (T.V.) and doubling time (D.T.) (days) have been evaluated as factors influencing patients's survival and therapy planning. 51 different parameters from these 114 pts have been stored and processed by an I.B.M. 370/158 computer. There was no statistical relationship between D.T. and stage, immune response, T.V., age, sex, etc. and histology although oat cell tumors tended to be faster. 77 out of 114 pts were followed until death. Eleven patients refused treatment 28 had surgical resection (ii of whom received adjuvant chemo- or radiotherapy) and 38 had only chemo and/or radiotherapy. A multivariate regression analysis (stepwise regression) showed that the most useful parameters to quantitate patients' survival were the D.T. (p < 0.0001) and the T.V. (p < 0.05); on the other hand when a patient's T.V. reached more than 500 cc death occurred imminently. According to these data were compdted the predicted survival in days (PS) according to this formula: PS=LOG (10xl0xl0) - LOG(D. x D 2 x D3)/ LOG2 (D., D^, D 3 = three dimensional measurements o~ a ~umor shadow). The PS for each patient correlated statistically to the observed one (OS) (R = 0.5853 - p<0.001) despite the treatment used. Stratifying the patients according to the given treatment PS correlated to the OS of the untreated patients (R=0.732 - p< 0.01) and those treated with chemo and/or radiotherapy (R=0.0685 - p < 0.0001); there was no statistical difference between survival of these two patient populations. The OS of resected patients did not correlate with their PS indicating that surgery modified the natural history of the disease. We conclude that stratification of patients on the basis of D.T. and T.V. is the best individual prognostic determinant of survival and can be used to identify patients who would benefit from a surgical resection when the TNM stage otherwise exclude this mode of therapy. Intermediate Filament Expression in Small Cell Lung Broersi , J.L.VI, Klein Rot I, ~., Wagenaar2, 1 Sj.Sc., Vooijsi , G.P., Carney , DN, Ramaekers , F . C . S . i . Dept. of Pathology, University of Nijmegen, The Netherlands. 2. Department of Pathology, St. Antoniushospital, Nieuwegein, The Netherlands, and 3. Department of Respiratory Diseases, Mater Misericordiae Hospital, Dublin, Ireland. Small cell lung carcinoma (SCLC) and carcinoid lung tumors were examined immunohistochemically for their intermediate filament protein content. Most SCLC and carcinoids showed a positive staining reaction with a polyclonal (cyto) keratin antibody and all were positive with a monoclonal antibody to cytokeratin 18, but negative with neurofilament antibodies. Since

Cancer.

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these data were in a p p a r e n t c o n t r a d i c t i o n with some reports in the literature we examined several lung cancer cell lines for their intermediate filament type(s)• On basis of, amongst others, radiosensitivity, D O P A - d e c a r b o x y l a s e a c t i v i t y and C - M y c - o n cogene e x p r e s s i o n the SCLC cell lines could be subdivided into two groups, i.e. the classic- and variant -type SCLC cell lines. The classic-type SCLC cell lines contain c y t o k e r a t i n s but no d e t e c t a b l e neurofilaments, while, in contrast, v a r i a n t - t y p e SCLC cell lines do not contain d e t e c t a b l e amounts of cytokeratins, but p a r t l y express n e u r o f i l a m e n t proteins. In the future the i d e n t i f i c a t i o n s of the intermediate filament content of SCLC and other lung cancers can help to d e t e c t the aggressive and t r e a t m e n t - r e s i s t a n t v a r i a n t - p h e n o t y p e in clinical specimens. M e m b r a n e and C y t o s k e l e t a l C o m p o s i t i o n o f lll~an Lung Cancers. Bernal, S., Stahel, R., Elias, A., Weinberg, K., Speak, J. D a n a - F a r b e r Cancer Institute and Harvard Medical School, Boston, Massachusetts, U.S.A. Murine m o n o c l o n a l antibodies (MoAbs) SMI, SM7, LAM2, LAM6, LAM7 and LAM8 are reactive with human lung cancers• SM7 is an IgGl, others are IgMs. Each a n t i b o d y reacts with d i f f e r e n t m e m b r a n e antigens• Most normal tissues, such as lung parenchyma, liver, kidney, adrenal and bone m a r r o w cells are unreactive. These MoAbs can detect cancer in bone marrow, which is not d e t e c t e d by c o n v e n t i o n a l stains. Clinical stage is often altered by results of antibody stain• These MoAbs, w i t h human complement, are s e l e c t i v e l y cytotoxic to lung cancers. Cell lysis o b s e r v e d include: SMI 99%; SM7 93%; LAM2 95%; LAM6 94%; LAM7 92%; LAM8 98%. E f f i c i e n c y of cell kill may be increased by the c o m b i n i n g several MoAbs. R e a c t i v i t y of MoAbs with lung cancer and ability to kill lung cancer cells suggest usefulness for e l i m i n a t i o n of cancer cells in bone m a r r o w prior to m a r r o w t r a n s p l a n t and p o s s i b l y for in vivo serotherapy. C y t o s k e l e t a l (CSK) c o m p o s i t i o n of human lung cancers was analyzed. Keratin and n e u r o f i l a m e n t was noted in small cell cancer. Small cell and non-small cell lung cancers appear to contain d i f f e r e n t m o l e cular forms of keratin. Studies on CSK c o m p o s i t i o n may help in diagnosis of h u m a n lung cancers and in tracing lineage. l'he Role of M e d i a s t i n o s c o p y (M) in the Preo p e r a t i v e S t a g i n g and S e l e c t i o n of Patients, With Small Ceil Ltmg C a n c e r (SCLC) for Surgery. Orel, J., Hrabar, B., Jerman, J. Department of Thoracic Surgery U n i v e r s i t y Medical Center, Ljubljana, Yugoslavia.

The role of M in the definitive p r e o p e r a t i ve staging og SCLC was evaluated in a retrospective study of 38 c o n s e c u t i v e patients who were c o n s i d e r e d potential candicates for resection on the basis of routine clinical and radiologic examination. In all the p a t i e n t s the disease was estimated as T1 or T2, NO, on the basis of roentgenograms made in two planes. Eighteen patients (47.4%) had a p o s i t i v e M, showing involvement i p s i l a t e r a l l y in ii, c o n t r a l a t e r a l l y in 3 and subcarinally in 6 cases. The result was p o s i tive in ii of 19 tumors located in the right lung, 7 of 19 tumors in the left lung, 14 of 27 tumors in the upper and middle lobes, and in 4 of ii tumors in the lower lobes. Five patients with a positive M were submitted to surgery, and in 2 o f these the process was unresectable, while in 3 resections were carried out. We o p e r a t e d upon 15 of 20 p a t i e n t s (52.6%) with a negative M; the p r o c e s s was unresectable in 2, and the tumors were removed in 13. On p o s t s u r g i c a l staging, the extent of the disease was identified as NO in 5, NL in 4 and N2 in 6 of the o p e r a t e d patients. The series p r e s e n t e d demonstrates that M alone is not a sufficiently reliable m e t h o d for the p r e o p e r a t i v e staging of SCLC, p r o v i d e d that N2 d i s e a s e is assumed unsuitable for resection. Six of 15 p a t i e n t s in the group with a negative M were improperly selected for surgery. We believe that a p r e l i m i n a r y CT scan of the mediastinum w o u l d indicate that anatomic location of the suspicious lymph nodes and increase the a c c u r a c y of the procedure. P r o g n o s t i c Factors in Small Cell Lung Cancer

(SCLC). 1 Groppl Havemann , K., Holle, R., , C , Klapsing 1 J., Becker, H., Dirks, P., Drings, P., Graubner, M., H~ssler, R, Hans, K., Hein, M., Mende, S., Pfannschmidt, G., Schroeder, M. i. D e p a r t m e n t of Haematology/Oncology, University of Marburg, Marburg, FRG. In a p r o s p e c t i v e m u l c i c e n t r e trial on the c o m b i n e d chemo- and radiotherapy of SCLC a set of b a s e l i n e d a t a from 305 patients were a n a l y z e d to assess the p r o g n o s t i c significance of these variables• In a c c o r d a n c e with the results of other studies, p e r f o r m a n c e status and extent of disease are identified as the most important factors, but in contrast to the literature loss of weight gives no additional prognostic information. Disease extent, usually c l a s s i f i e d into limited vs. extensive disease, may be improved for p r o g n o s t i c p u r p o s e s by a further s u b d i v i s i o n of the "extensive" category. Distant metastases, e s p e c i a l l y bone marrow, liver and bone, leads to a significantly (p < 0.01) worse prognosis in p a t i e n t s with extensive disease (7.5 months m e d i a n survival vs. 11.5 months). Prognosis is m u c h better for female patients than for male, e s p e c i a l l y when long-term survival is c o n s i d e r e d with estimated 2-year-survival rates of 14% vs. 3% (p < 0.01). Another