Potential role of bcl-2 as a suppressor of tumour angiogenesis in non-small-cell lung cancer.
It has been reported that genes regulating apoptosis may play a role in tumoral angiogenesis. This study examined the relationship between tumour vascularization, a measure of tumour angiogenesis, and bcl-2 and p53 expression in operable non-small-cell lung cancer (NSCLC). The relationship 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, p53, 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 between c-erbB-2 expression and vascular grade. However, in bcl-2-negative 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 in regulating tumour angiogenesis. Since normal lung epithelium expresses bcl-2, a sequence of tumour progression involving loss of bcl-2, then activation of c-erbB-2 or increase in tumour vascularization is proposed.
Koukourakis
M I
MI
ICRF Medical Oncology Unit, Radcliffe Hospital, Oxford, UK.
Giatromanolaki
A
A
O'Byrne
K J
KJ
Whitehouse
R M
RM
Talbot
D C
DC
Gatter
K C
KC
Harris
A L
AL
D000368:Aged; D000704:Analysis of Variance; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D019254:Genes, bcl-2 / Q000502:physiology*; D016158:Genes, p53 / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D012189:Retrospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases