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Interferon-_ and gamma (IFN_ and gamma) caused significant but slight growth inhibition over a 7&y incubation period. However, none of tie other 6 cytokines, tumor necrosis factor (l?lF), lymphotoxin 0, interleukin- Ill (IL- lB), interleukin-2 (IL-2). transforming growth factor-61 i.TGF-6l),orgranulocytecolony-stimulatingfactor(G-CSF), modifiedSCLCcellpmliferation. Incontmst,all 1Olinesweresensitive to lysis by natural killer (NK) and lymphokine-activated killer (LAK) cells. Sensitivity to LAK cells could be increased by pretreatment of SCLC cells with IFN-gamma. As resistance to the cytostatic/cytotoxic activity of some cytokines has been associated with auto&e pmduc- tion of cytokines, we screened the SCLC lines for cytokine mRNAs. Within the limits of detection of the assay we found no expression of TNF, TGF-81, IL-16 or IL-6 mRNA in the 10 SCLC lines.

Expression of blood-group antigen A - A favorable prognostic factor in non-small-cell lung cancer Lee JS, Ro JY, Sahin AA, Hong WK, Bmwn BW, Mountain CF. et al. Department of Medical Oncology, Box 80, MD. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. New Engl J Med 1991:324:1084-90.

Background. New prognostic factors are needed to guide the treat- ment of patients with non-small-cell lung cancer. We evaluated the prognostic value of altered expression of ABH blood-group antigens, which has been implicated in the multistep process of carcinogenesis and tumor progression. Methods. Tbe presence of blood-group antigens was assessed immtmohistochemically in paraffin-embedded tumor samples from 164 patients who underwent curative surgery for non- smallcelllungcancer fmm 1980 through 1982. Monoclonalantibodies were used to detect the A and B antigens, and Ulex europaeus agglutinin 1 to detect H antigen. Results. Survival of the 28 patients with blood type Aor AB who had primary tumors negativeforblood-groupantigen A was significantly shorter than that of tbe 43 patients with antigen A- positive tumors (P ~0.001) and of the 93 patients with blood type B or 0 (P = 0.002). The respective median survival times were 15,71, and 39 months. Disease progressed significantly earlier in the 28 patients with tumors negative for blood-group antigen A than in the antigen A- positive patients (P < 0.001). Expression of blood-group antigen B or H in tumor cells did not correlate with survival. Cox proportional-hazards regression analysis showed that expression of blood-group antigen A in tumor cells added significantly to the prediction of overall survival provided by other known prognostic factors among the patients with blood type A or AR (P = O.M)4). Conclusions. Expression of blood- group antigen A in tumor cells is an important favorable prognostic factor in patients with non-small-cell lung cancer. This variable needs to be considered in the design of future trials of therapy.

Specific inhibition of K-ras expression and tumorigenicity of lung cancer eelIs by antisense RNA Mukhopadhyay T, Tainsky M, Cavender AC, Roth JA. University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Bouk?vardlBox 109. Houston. TX 77030. Cancer Res 1991;51:1744-8.

A human lung cancer cell line (H46Oa) with a homozygous sponta- neous K-ras mutation was transfected with a recombinant plasmid that synthesizes a 2-kilobase genomic segment of the K-ras pmtooncogene in antisense orientation. Translation of the mutated K-ras mRNA in H46Oacells wasspecificallyinhibited, whereasexpressionofH-rasand N-ras was unchanged. A 3-fold growth inhibition occurred in H46Oa cells when expression of the mutated ras p21 protein was down- regulated by antisense RNA. However, cells remained viable despite the absence of K-ms expression. The growth of H46Oa tumors in nuAm mice was substantially reduced by expressed K-ras antisense RNA.

Flow cytometric measurement of ~53 protein expression and DNA content in paraffin-embedded tissue from bronchial carcinomas Morkve 0,Laerum OD. Gade Institute, Dept. ofPathology, H&eland Hospital, N-5021 Bergen. Cytometry 1991;12:438-44.

The nuclear protein p53 has been measured in archival lung cancer biopsies.ThemonoclonalantibodyPAb 1801, whichrecognizes human

~53, was used. After immunostaining, the nuclei prepared from paraf- tin-embedded tissue were stained witb propidium iodide for simultane- ous measurement of DNA content: 17 of 24 lung cancers were pS3 positive. The S-phase fraction in positive tumors was 22.9 f 6.4%. as compared to 13.6 f 6.1% in negative tumors (P < 0.02). In ten of the positive ttmmrs (two small cell carcinomas and eight non-small cell carcinomas), me ~53 expression varied through cell cycle, whereas in seven tumors (five small cell carcinomas and two non-small cell carcinomas), no such variation of p53 expression was observed. Freez- ing the nuclear suspensions did not substantially reduce the p53 signals. Control experiments with the SV40-transformed human foreskin fi- bmblast cell line HSF4-T12 showed that the enzymatic digestion utilized to dissociate paraffin-embedded tissue did not significantly reduce ~53 fluorescence. Immunohistochemical staining of biopsy specimens indicated that only cancer cells were overexpressing ~53. In conclusion. using themonoclonal antibody PAb 1801, ~53 isdetectable in cell nuclei prepared fmm paraftin-embedded bronchial carcinoma bioipsies. P53 positive tumors have increased proliferative activity compared to ~53 negative tumors. Furthermore, the lack of cell cycle variation of ~53 in small cell carcinomas indicates that this pattern may be related to high-grade malignancy.

Pathology Neural cell adbesion molecule expression, neuroendocrine differen- tiation and prognosis in lung carcinoma Kibbelaat RE, Moolenaat KEC, Michalides RJAM, Van Bodegom PC, Vanderschueren RGJRA, Wagenaat SS, et al. Department of Pathol- ogy. The Netherlands CancerInstitute, Plesmanlaon 121,1066 CXAm- sterdam. Eur JCancer 1991;27:431-5.

We investigated tbe expression of the neural cell adhesion molecule (NCAM) in a series of surgically resected lung carcinomas of various histological subtypes by means of a panel of monoclonal antibodies recognising different N-CAM epitopes. In a subgroup of 56 turnours, the results of immunostaining with MAb 123C3 - the antibody studied most extensively in our material - were compared to the ulnastructure, and in 23 1 radically resected non-small ccl1 carcinomas, with histologi- cal tumour type and with clinical follow-up data. N-CAM expression was not limited to neuroendocrine turnouts, as assessed ultmstmctu- rally. Non-small cell lung carcinomas positive for MAb 123C3 showed post-operative overall and disease-free survival times significantly shorter than 123C3negative non-small cell carcinomas.

Clinical assessment

A case of increased ‘*WMP uptake in adenocarcinoma of the lung SuematsuT,Yosbi&S,YamamotoH,MarmaT,OgawaK,KomotoE, et al. Department of Radiology, Hyogo Medical Center fir Adults, Nishinomiya: Jpn J Nucl Med 1991;28:293-6.

It has been reported (hat delayed LUI-IMP lung scintigraphy shows a defect corresponding to the tumor with increasedaccumulation around the tumor, and that au increased accumulation is associated with atelectasis and inlIammation. We presented a case of increased uptake of “‘I-IMP in lung cancer. None of the other reported case of incmased uptake in lung cancer, to out knowledge, occurred. A Z&year-old man had a 6 cm mass in the lower lobe of the right lung. Cytologic examination with a small curette diagnosed the case as an adenocar- cinema. The ‘%IMP scintigraphy was performed 24 hours after intravenous injection of 111 MBq of ‘“I-IMP. The ‘“I-IMP SPEiCT lung images showed an area of increased L”I-IMP concentration corre- sponding to the tumor mass. The patient’s subsequent course was characterizedby massive pleural effusion caused by extensive invasion to the pleura despite chemotherapy. He died about 2 months after the lUl-IMP scintigraphy. The right lung removed at necropsy confmed that the area of high rUl-IMP concentration corresponded to the mass, which proved a poorly differentiated adenocarcinoma. One should note that there is an unusual case with high ‘231-IMP uptake in lung cancer.