POTENTIAL ROLE OF BCL-2 AS A SUPPRESSOR OF TUMOR ANGIOGENESIS IN NON-SMALL-CELL LUNG-CANCER

It has been reported that genes regulating apoptosis may play a role i n tumoral angiogenesis. This study examined the relationship between t umour vascularization, a measure of tumour angiogenesis, and bcl-2 and p53 expression in operable non-small-cell lung cancer (NSCLC). The re lationship between bcl-2, p53 and tumour vascularization and epidermal -growth-factor-receptor(EGFR) and c-erbB-2 expression was also studied . Tissue sections from resected tumour specimens of 107 NSCLC patients were evaluated immunohistochemically for vascular grade and bcl-2, p5 3, EGFR and c-erbB-2 expression, bcl-2 expression was found in 20/107 (19%) cases and was associated with squamous-cell histology (p = 0.03) , A strong inverse relationship was found between bcl-2 expression and vascular grade (p = 0.005), All c-erbB-2-positive cases were negative for bcl-2 expression (p = 0.01). Overall no association was found bet ween c-erbB-2 expression and vascular grade. However, in bcl-2-negativ e cases positive c-erbB-2 expression correlated with low angiogenesis (p = 0.05), No relationship was found between p53 and EGFR expression and bcl-2, c-erbB-2 or vascular grade, The improved prognosis reported in bcl-2-positive NSCLC may be related to low tumour vascularization, The results suggest that the anti-apoptotic gene bcl-2 plays a role i n regulating tumour angiogenesis, Since normal lung epithelium express es bcl-2, a sequence of tumour progression involving loss of bcl-2, th en activation of c-erbB-2 or increase in tumour vascularization is pro posed. (C) 1997 Wiley-Liss, Inc.