Angiogenesis and apoptosis-related protein (p53, bcl-2, and bax) expression versus response of gastric adenocarcinomas to paclitaxel and carboplatin chemotherapy.
The role of angiogenesis and apoptosis-related proteins in defining response to chemotherapy is poorly understood. We examined the microvessel density (MVD) and the expression of p53, bcl-2, and bax proteins in a series of 28 locally advanced gastric adenocarcinomas, treated with paclitaxel and carboplatin. A strong cytoplasmic reactivity in more than 10% of cancer cells was recorded in 25% of cases for p53 protein, and in 14% and 64% of cases for bcl-2 and bax proteins, respectively. Microvessel density was assigned in three categories: low (<35), medium (35-60), and high (>60). Tumors of medium MVD showed a significantly higher response rate compared with those of high or low MVD (p = 0.01 and 0.001, respectively), and prognosis was significantly better in this group of patients with medium MVD tumors (p < 0.02). Loss of bax protein expression was somewhat more frequent in tumors resistant to chemotherapy, but this difference was not of statistical significance. Nuclear p53 reactivity was associated with higher MVD (p = 0.02). The expression of p53 and bcl-2 did not influence the outcome of treatment. The present study suggests that although apoptosis-related proteins may have a role in defining response to taxanes, parameters related to tumors' vasculature, such as drug availability or angiogenic tissue regeneration, may be equally important.
Giatromanolaki
A
A
Tumour and Angiogenesis Research Group, Iraklion, Crete, Greece.
Stathopoulos
G P
GP
Koukourakis
M I
MI
Rigatos
S
S
Vrettou
E
E
Kittas
C
C
Fountzilas
G
G
Sivridis
E
E
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D016190:Carboplatin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D017239:Paclitaxel / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D016190:Carboplatin; D017239:Paclitaxel