Abstracts/Lung Cancer 13 (1995) 185-232 203

Mutated K-ras gene analysis in a randomized trial of preoperative chemotherapy plus surgery versus surgery in Stage IIIA non-small cell lung cancer Rose11 R Molina F, Moreno I, Martinez E, Pifarre A, Font A et al. Deportment of Medical Oncology Deportment ofMedical Oncology Hospital Germans Trias i Pujoi, Box 72, 08916 Badalona, Barcelona. Lung Cancer (Ireland) 1995;12:Suppl l:S59-S70.

The observation that the proteins encoded by ras genes play a central role in the signalling pathways usedby cells to respond to growth factors and the fact that mutated ras proteins are constantly promoting cell division have led to a PCR-based hunt for additional clinical information. In the present study, K-ras analysis draws the following conclusions: (1) K-ras point mutation frequency was higher in the surgery group (10 of 24 patients) than in the chemotherapy-surgery group (3 of 20 patients). (2) Mutated K-ras was predominantly observed at codon 12 but live mutations appeared at codon 6 1. (3) Mutations were identified in the squamous cell carcinoma histological NSCLC subtype except in four cases corresponding to adenocarcinoma. (4) A multivarious pattern of substitutions, especially at codon 12, were noted with aspartic K 12 substitutions more prone to develop bone metastases. (5) Although a genotypic K-ras classification of NSCLC may not yet be formulated, our accumulated data (unpublished) suggest a trend toward it. (6) Patients with mutated K-ras tumors in the surgery group had no different survival than those with normal K-ras. However our pooled data as well as other authors’ results assert that mutated K-ras constitute an additional prognostic datum that deserves to be included together with TNM classification. In the design of new preoperative (neoadjuvant) chemotherapy trials, stratification of tumors by K-IX status deserves to be further investigated in order to correlate with response, relapse and survival, Mutated K-ras genotype merits further research. Finally, the paradigm ofuneven histological distribution and mutated K-ras spectra among researchers should serve as a stimulus to search for further contributions in this field.

Prognostic factors in NSCLC. Recent experiences Van Zandwijk N, Mooi WJ, Rodenhuis S. Department of Chest Oncology* The Netherlands Cancer Institute, Antoni wan Leeuwenhoek Huis, Plesmonloon 121, I066 CXAmsterdam. Lung Cancer (Ireland) 1995;12:Suppl l:S27-S33.

In recent years, a group of new prognostic factors have been added to the list of well-known clinical prognostic factors of non-small cell lung cancer. Among these are mutations in the K-ras oncogene, abnormalities in ~53, the presence of N-CAM expression as measured by Mab immunostaining and elevated serum levels of NSE. These fhctors have provided important clinical insights into the biology of lung cancer and prospective studies using these biomarkers are now warranted to provide further important clues about their potential significance in treatment selection of patients,

Biological prognostic factors in non-small cell lung cancer Scagliotti GV, Masiero P, Pozzi E. Universi& of Torino. Dept. of Clin.1 BiologicalSciences, S. Luigi Gonsaga Hospital, Orbassono. 7iuin. Lung Cancer (Ireland) 1995;12:Suppl l:S13-S25.

The results of conventional treatments for lung cancer remain poor and long-term survival rates have changed little over the last 10 years. In the same period of time there has been an explosion in the knowledge on the processes of cellular transformation, tumour progression, invasion and metastasis. The major categories of biological events implicated in non-small cell lung cancer include growth factor receptors expression (epidermal growth factor receptor, pl85(c-neu)), autccrine growth factor production (transforming growth factor G), dominant oncogenes

activation (ras genes) and deletion of tumour suppressor genes (p53 gene, retinoblastoma gene) and these are some of the abnormalities associated with specific histological types and with poor prognosis. Additional prognostic information can be obtained from the evaluation of the ploidy and proliferative activity of the tumours, carbohydrate antigens expression presence of neuroendocrine dilferentiation and the evaluation of markers of the sequential steps involved in the process of turnour dissemination,

Bronchoalveolar lavage in the diagnosis of disseminated lung tumors Poletti V, Romagna M, Allen KA, Gaspnni A, Spiga L. Deportment of Pulmonary Medicine, Ospedale Maggiore, Lotgo Nigrisoli 2, 40133 Bologna. Acta CytoI 1995;39:472-7.

We repott our experience with bronchoalveolar lavage (BAL) and its value in the diagnosis of malignant lung inflhrates. A total of 162 patients with biopsy- or autopsyproven cancer had an analysis of BAL fluid performed. Cytologic examination showed malignant cells in 123 (76%) patients. The diagnostic accuracy varied depending on the neoplastic nature and growth pattern of the disease. BAL disclosed cancer cells in 93%of44 btonchioloalveolar carcinomas. Carcmomatous lymphangitis due to metastatic cancer was diagnosed in 83% of 69 cases. Hematogenous metastases (with sharply circumscribed nodules on chest radiography) were diagnosed in 45% of 22 such cases. We recognized 67% of 15 non-Hodgkin’s lymphomas and 3 of 9 cases of Hodgkin’s disease with pulmonary involvement Immunocytochemistry using monoclonal and/or polyclonal antibodies was of value in the identification and classification of cells in non-Hodgkin’s lymphoma.

Malignant pleurisy and intrathoracic dissemination in carcinoma of the lung: Diagnostic, therapeutic and prognostic implications Ishida T, Kohdnno S, Hamatake M, Fukyama Y, Tateishi M, Sugimachi K et al. Department of Surgery IIs Faculty of Medicine, Kyushu University, 3-l-I Maidashi, Higoshi-ku. Fukuoko 812. In1 Surg 1995;80:70-4.

GfT, disease of lung cancer, malignant pleurisy and intrathomcic dissemination are the greatest factor preventing a cure, despite the best efforts of surgery and various adjuvant therapy modalities. Preoperative evaluation of this disease is of first importance using conventional radiology and computed tomography. Gf the 43 patients who were intraoperatively diagnosed to be the disease, 8 (18%) appeared on the conventional radiology as small amounts of pleural effusion, and 9 (2 1%) with a interlobar pleural thickening. Based on CT findings, 16 (67%) had one or more of some disseminated nodules, interlobar pleural thickening and broad pleural indentation. In Patients with T, disease, the 5year survival rate was 14% in patients with malignant pleurisy and/or intrathoracic dissemination, compared with the 18% in those with direct invasion to great vessels, with no sign&ant difference. According to intrapleural instillation as postoperative adjuvant therapy, the 5-year survival rate was 25% in the patients given interleukin-2, compared with 38 months of survival time for patients prescribed doxorubicin and 33 months for those underwent exploratory thoracotomy. A more favorable prognosis of patients whose malignant pleurisy and/or intrathoracic dissemination are first found at thoracotomy can be expected when postoperative intrapleural instillation of interleukin-2 is prescribed following the resection of the intrathoracic tumors.