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• W2233887450 abstract "The International Adjuvant Lung Cancer Trial (IALT) demonstrated an absolute survival rate benefice of cisplatin based chemotherapy of 4 % in surgically treated patients with non small cell lung carcinoma (NSCLC). To identify immunohistochemical biomarkers which correlate differently with survival in the chemotherapy and observation group (predictive analysis) we collected 867 paraffin blocks from 28 centers and made a histopathological review allowing selection of 783 tumors recorded as NSCLC with pathological parameters. These tumors came from 401 chemotherapy treated and 382 observation patients. Our aim was to evaluate the potential prognostic and predictive role of 3 non mitochondrial apoptotic factors, the death receptor Fas, its ligand FasL and survivin a G2-M cell cycle regulated protein with anti-apoptotic properties. Immunohistochemical analysis was performed on 783 paraffin sections with automated immunostainer Ventana using specific polyclonal antibodies Fas C20 and FasL N20 (Santa Cruz) and survivin R&D. Staining scores (0-300) were obtained by multiplication of the percentage of labeled cells by intensity of staining (1-3). The cut off score for discriminating positive from negative cases was 240 for Fas and FasL and 60 for survivin. Prognostic and predictive analysis was based on a Cox model adjusted on stage, type of surgery, histology, lymphoid infiltration, pathological N status, WHO performance status, age, sex, and center. Only p values below 0.01 were considered as significant. Fas and FasL immunostaining were cytoplasmic and membranous. Of 773 exploitable cases with positive internal controls (normal epithelial cells of a score 240-300) 73 % were Fas negative, 49 % FasL negative. Taking germinal cells as positive control 54 % of cases were survivin positive. Fas and FasL were positively correlated (distribution and intensity) with a Spearman's correlation of 0.43 (p≤0.0001). Survivin did not correlate with Fas, FasL or P53. In a logistic model with all variables, Fas positivity correlated with vascular invasion (p=0.006; lower in vascular invasion) and WHO status (p=0.008; higher in low WHO). FasL correlated with histology (p≤0.0001; higher in adenocarcinoma) and pleural invasion (p=0.04). Survivin was lower in adenocarcinoma (p≤0.0001), higher in males (p=0.0001) and lower in older patients (p=0.009). Fas, FasL, and survivin scores were not related to prognosis but the ratio of a Fas to FasL > or = 1 was related to longer survival (HR=0.72; p=0.02). None of these markers had predictive value for chemosensitivity at the level of significance 0.01. However, a borderline significant interaction was observed, chemotherapy being more efficient for FasL negative (HR=0.69) as compared with FasL positive (HR=1.03; p=0.06), as well as for Fas:FasL ratio >1 (HR=0.51) as compared with a ratio of 1 (HR=1.13) or a ratio ≤1 (HR=0.80; p=0.05). Two non mitochondrial related apoptotic factors of the death receptor pathway have borderline predictive value (FasL and Fas/FasL). The benefit of chemotherapy was observed among FasL negative patients and those with Fas:FasL ratio > 1. Current research is ongoing to pool these results with other adjuvant trial populations in order to validate their use in selecting patients for cisplatin-based chemotherapy." @default.
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• W2233887450 title "PD2-3-4: Prognostic and predictive value of apoptosis related factors Fas, FasL and survivin in non small cell lung carcinoma patients enrolled in the IALT Trial" @default.
• W2233887450 doi "https://doi.org/10.1097/01.jto.0000283366.53929.20" @default.
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