Background: Lung cancer in the female population is a growing sanitary problem. Gender-related differences in susceptibility, pathogenesis and possible cure for this disease are interesting fields of basic and clinical investigation. Female sex, adenocarcinoma histology, non smoking history represent clinical features correlated with response to EGFR-TKIs. The use of these molecules in patients selected on a "clinical enrichment" basis are warranted. Patients and Methods: The mutational status of EGFR (exons from 18 to 21) and K-ras (exon 1) is routinely evaluated in patients with adenocarcinoma of the lung referred to our Institution. From January 2006 30 women with advanced NSCLC were observed: median age 60 yrs (37-80); smokers=12 pts (40%); non smokers=18 (60%). Adenocar-cinoma= 22 pts (73.3%); BAC =6 (20%); adenocarcinoma with BAC features= 2 (6.7%). Fifteen pts (50%) had stage IV disease at diagnosis and 5 of them (33.3%) showed brain metastases. Results: 9/30 (30%) EGFR mutations were detected: 5 in exon 19; 2 in exon 21; 2 in exon 20. 3/30 (10%) K-ras mutations were noted. 11 patients received TKIs (Gefitinib 250 mg/die or Erlotinib 150 mg/die orally) as second-line therapy for at least 2 months and were evaluable for activity: 5 PR (45%) and 6 PD (55%) were observed. All responding patients were non smokers; 3 had mutation in exon 19, 1 in exon 21 and 1 had Wild Type EGFR. All were WT K-ras. Among patients with PD: 1 had tumor with mutation in exon 21, 2 had tumors with K-ras mutation and 3 WT EGFR. Median progression-free survival was 5 months (range 2-14+ months); median overall survival was 27 months (range 8-108 months). Conclusions: In our "clinically enriched" population (women with adenocarcinoma) we can observed that: 1) 60% of patients were non smokers; 2) 17% had brain metastases at diagnosis; 3) the frequence of EGFR mutations is 30% (higher than that reported in caucasian non selected series); 4) the most frequent EGFR mutation was in exon 19. In patients receiving second-line TKIs response rate was 45%; all responding patients were non smokers and 4/5 (80%) had tumors with EGFR mutations. The study is ongoing. Updated results will be presented at the meeting.

Despite chronic inflammation and the presence of hypergammaglobulinemia, rheumatoid factor (RF) is rarely found in the blood of patients with ankylosing spondylitis (AS). We used ELISA to compare spontaneous and pokeweed mitogen (PWM)-induced IgG, IgM and IgM rheumatoid factor (IgM-RF) production in normals and in patients with rheumatoid arthritis (RA) and AS. The IgG and IgM synthesis in these three groups did not differ. However, the IgM-RF level in PWM-induced mononuclear cell cultured supernatants of AS was significantly decreased, compared with normal and RA patients. Furthermore, mixing experiments by co-culture of normal T or B cells with patient's B or T cells in the presence of PWM revealed a deficiency of the helper T cell function in patients with AS. These results illustrate the cellular mechanism of the seronegativity of the rheumatoid factor in patients with ankylosing spondylitis.