84 CHAPTER 20 Lung Cancer, 4 (1988) 84-86 Elsevier NEUROENDOCRINE AND EPITHELIAL DIFFERENTIATION ANTIGEN EXPRESSION IN NEWLY DIAGNOSED SMALL CELL LUNG CANCER H.H. Berendsen', L. de Ley', P.E. Postmus", S. Poppema"', H.J. Sluiter", T.H. The" "Dept. of Clinical Immunology, "*Dept, of Pulmonology, "'*Dept. of Pathology, University Hospital, Groningen, The Netherlands. This study was supported by a grant of the Koningin Wilhelmina Fonds. Correspondence to H.H. Berendsen, Dept. Clinical Immunology, University Hospital, Oostersingel 59, 9713E2 Groningen, The Netherlands. ABSTRACT A panel of monoclonal antibodies (Moab) directed against antigens related to a neuroendocrine and epithelial differentiation state, have been prospectively applied to small cell lung cancer (SCLC) biopsy specimens obtained before the induction of polychemotherapy. No differences in panel reactivity were noted between partial and complete responders, Neuroendocrine differentiation antigens were not expressed in two patients who failed to respond to the induction regimen. A third SCLC specimen without neuroendocrine differentiation antigens, was obtained from a curatively resected patient. This indicates that SCLC without neuroendoorine differentiation antigens comprises a group of tumours mimicking non-SCLC. INTRODUCTION With combination chemotherapy tumour regression is obtained in 80-90% of SCLC patients. Despite the fact that, not infrequently, a clinical complete response is obtained most patients eventually die from the development of drug resistant SCLC and only very few patients can be cured with current drug regimens I Morphologic subtyping of SCLC according to the WHO subclassifications of 1967 and 1981 has revealed no prognostic significance and it is uncertain how far such subtyping should be attributed to artefacts during the diagnostic work-up2 The identification of the drug resistant phenotype of SCLC is far from complete and further characterisation of the resistant tumour cells is necessary to guide new treatment modalities. In vitro studies have revealed the so called "variant" SCLC cell lines which have been proposed to represent the in vitro counterpart of therapy resistant SCLC. "Variant" cell lines have a shorter doubling time and are more refractory to radiation induced cell kill3,4. It remains to be established whether these in vitro findings reflect tumour properties in the in vivo situation. In SCLC, antigens are present which are shared by normal neuroendocrine tissues. This is in agreement with a neuroendocrine differentiation programme of SCLC. We have looked whether neuroendocrine differentiation antigens were equally encountered in different clinical categories of newly diagnosed SCLC patients. MATERIALS AND METHOD~; Patients Immunohistological staining was performed on 30 biopsies obtained from untreated patients with histologically proven SCLC who were evaluable for response. An additional biopsy from a patient not responding to chemotherapy, was obtained on restaging immediately after 5 cycles of doxorubicin, cyclophosphamide and etoposide. One tumour specimen was obtained from a patient who was curatively resected, did not receive adjuvant chemotherapy and is alive and well without signs of recurrence 60 weeks after surgery. Staging procedures included roentgenograms and tomography of the chest, fibreoptic or rigid bronchoscopy, blood cell counts, serum electrolytes, liver and renal function tests, ultrasound of the abdomen, isotope bone scans, bone marrow biopsies from bilateral posterior lilac crests, and neurological investigation. Restaging procedures included roentgenograms and tomography of the chest, fibreoptic or rigid bronchoscopy and all initially abnormal investigations were repeated. All patients received an induction therapy with 5 cycles of either Z ~ositive $:alnlng 100 9g 8g ?g 60 5g 4G 30 2g lg O MOC-1 MOC-52 MOC-21 MOC-32 MOC-51 Figure 1 : Neuroendocrine differentiation antigens in SCLC and response to induction polychemotherapy. [] ©o~plete ~espoflde~s n=8 0 partial ~esponde~s n=28 0169-5002/88/$03.50 © 1988 Elsevier Science Publishers B.V. (Biomedical Division)