Hypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas.
Hypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas.
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DOI：
10.1038/sj.bjc.6603524
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发表时间：
2007-01-15
影响因子：
8.8
通讯作者：
West, C M L
中科院分区：
文献类型：
--
作者：
Griffiths, E A;Pritchard, S A;Valentine, H R;Whitchelo, N;Bishop, P W;Ebert, M P;Price, P M;Welch, I M;West, C M L
研究了缺氧诱导因子-1 (HIF-1)α在胃癌发生序列中的表达，并作为手术切除的胃和胃食管交界肿瘤的预后因素。用免疫组化方法检测正常黏膜（n=20）、幽门螺杆菌相关性胃炎（n=24）、肠化生（n=24）、不典型增生（n=12）、肠（n=19）和弥漫腺癌（n=21）的蛋白表达。研究了177例胃和胃食管交界区腺癌切除标本中HIF-1α表达与预后的关系。缺氧诱导因子-1α在正常胃粘膜中未见表达，但随着幽门螺杆菌相关性胃炎、肠化生、不典型增生到腺癌的进展，其密度和强度均增加（P<0.01）。切除标本中49例（28%）呈局灶性阳性，41例（23%）呈浸润性肿瘤边缘染色。侵袭性边缘表达与淋巴结转移（P=0.034）、TNM晚期（P=0.001）相关，是癌症特异性生存的不良预后因素（P=0.019）。在单因素分析中，与不表达HIF-1α的肿瘤相比，浸润性边缘染色与1.6 （95% CI 1.0 - 2.5）相关，局灶阳性染色与0.7 （95% CI 0.5 - 1.2）相关。缺氧诱导因子-1α在多因素分析中失去预后意义。结果表明，HIF-1α参与胃癌的发生和疾病进展，但仅是生存的一个弱预后因素。
Hypoxia-inducible factor-1 (HIF-1)α expression was studied in the gastric carcinogenesis sequence and as a prognostic factor in surgically resected gastric and gastro-oesophageal junction tumours. Protein expression was examined using immunohistochemistry on formalin-fixed biopsies of normal mucosa (n=20), Helicobacter pylori associated gastritis (n=24), intestinal metaplasia (n=24), dysplasia (n=12) and intestinal (n=19) and diffuse (n=21) adenocarcinoma. The relationship between HIF-1α expression and prognosis was assessed in resection specimens from 177 patients with gastric and gastro-oesophageal junction adenocarcinoma. Hypoxia-inducible factor-1α expression was not observed in normal gastric mucosa but increased in density (P<0.01) and intensity (P<0.01) with progression from H. pylori-associated gastritis, intestinal metaplasia, dysplasia to adenocarcinoma. The pattern of staining in the resection specimens was focally positive in 49 (28%) and at the invasive tumour edge in 41 (23%). Invasive edge expression was associated with lymph node metastases (P=0.034), advanced TNM stage (P=0.001) and was an adverse prognostic factor for cancer-specific survival (P=0.019). In univariate analysis and in comparison with tumours not expressing HIF-1α, invasive edge staining was associated with a hazard ratio of 1.6 (95% CI 1.0−2.5) and focally positive staining a hazard ratio of 0.7 (95% CI 0.5−1.2). Hypoxia-inducible factor-1α lost prognostic significance in multivariate analysis. The results suggest HIF-1α is involved in gastric carcinogenesis and disease progression, but is only a weak prognostic factor for survival.