Potential role ofbcl-2 as a suppressor of tumour angiogenesis in non-small-cell lung cancer

Abstract

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. Int. J. Cancer 74:565–570, 1997.© 1997 Wiley‐Liss, Inc.

Relation of hypoxia inducible factor 1α and 2α in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival

“…HIF2α was higher in cases with high or low MVD but was significantly lower in cases with a medium degree of vascularization. This U-like-shaped association of HIF2α with MVD is in accordance with previous studies of ours where not all VEGF-, TP-or bFGF-expressing tumours show an increase in angiogenesis (Koukourakis et al, 1997b(Koukourakis et al, , 2000Giatromanolaki et al, 1998Giatromanolaki et al, , 2000. We suggest that although hypoxia triggers the expression of a cascade of angiogenic factors through HIF stabilization, the process of angiogenesis is subject to other modulators.…”

Expression of Bcl-2 predicts outcome in locally advanced non-small cell lung cancer patients treated with cisplatin-based concurrent chemoradiotherapy

“…This speculation may explain the responsiveness of tumors with high Bcl-2 expression to chemotherapy or RT. Finally, several studies showed that high expression of Bcl-2 is associated with low tumor vascularization in NSCLC probably by suppression of angiogenic factor such as vascular endothelial growth factor, suggesting the correlation with better outcome [43][44][45][46]. However, further studies are essential to prove these suppositions.…”

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis

“…Ten were excluded (Giatromanolaki et al, 1996a(Giatromanolaki et al, ,b, 1997Koukourakis et al, 1997Koukourakis et al, , 1999Koukourakis et al, , 2000aKakolyris et al, 1999) because identical cohorts of patients were used in other selected publications. In the eight remaining eligible studies (Apolinario et al, 1997;Kawaguchi et al, 1997;Pastorino et al, 1997;Duarte et al, 1998;Ohta et al, 1999;O'Byrne et al, 2000;Han et al, 2001;Hasegawa et al, 2001), published between 1996 and 2001, the total …”