Giatromanolaki A, Koukourakis M I, Gatter K C, Harris A L, Sivridis E
Department of Pathology, Democritus University of Thrace, Alexandroupolis 68100, Greece.
J Clin Pathol. 2008 Feb;61(2):217-20. doi: 10.1136/jcp.2007.046680. Epub 2007 May 18.
BNIP3 is a pro-apoptotic mitochondrial protein induced under hypoxic stress, with the BNIP3 gene being under direct regulation of the hypoxia-inducible HIF-1alpha transcription factor. Induction of BNIP3 leads to caspase-independent necrosis-like cell death and an aggressive tumour phenotype. The role of BNIP3 in endometrial cancer was examined.
The immunohistochemical patterns of BNIP3 expression in 72 early endometrial adenocarcinomas of the endometrioid cell type were studied. Correlation of BNIP3 with the hypoxia-inducible factor HIF-1alpha pathway and with prognosis was also examined.
BNIP3 was strongly and extensively expressed in the cytoplasm of cancer cells in 23/72 (31.9%) cases. This high BNIP3 reactivity was not related to histological grade, depth of myometrial invasion or steroid hormone receptor expression. There was, however, a significant association of BNIP3 reactivity with HIF-1alpha (p = 0.04), VEGF (p = 0.04) and, particularly, LDH-5 expression (p = 0.0001). Furthermore, high BNIP3 was associated with poor survival in both univariate (p = 0.05) and multivariate (p = 0.03) models.
BNIP3 seems to be an important hypoxia-regulated molecule involved in endometrial cancer pathology. Given that high BNIP3 reactivity, being linked with poor post-operative outcome, has been linked with a favourable response to cytotoxic therapy (as previously indicated in experimental studies), high BNIP3 expression may be an indicator for adjuvant chemoradiotherapy in stage I endometrial carcinomas.
BNIP3是一种在缺氧应激下诱导产生的促凋亡线粒体蛋白，BNIP3基因受缺氧诱导的HIF-1α转录因子直接调控。BNIP3的诱导导致不依赖半胱天冬酶的坏死样细胞死亡和侵袭性肿瘤表型。本研究检测了BNIP3在子宫内膜癌中的作用。
研究72例子宫内膜样细胞类型的早期子宫内膜腺癌中BNIP3表达的免疫组化模式。还检测了BNIP3与缺氧诱导因子HIF-1α途径及预后的相关性。
在23/72（31.9%）例病例中，癌细胞胞质中BNIP3呈强而广泛的表达。这种高BNIP3反应性与组织学分级、肌层浸润深度或类固醇激素受体表达无关。然而，BNIP3反应性与HIF-1α（p = 0.04）、VEGF（p = 0.04），尤其是LDH-5表达（p = 0.0001）存在显著相关性。此外，在单因素（p = 0.05）和多因素（p = 0.03）模型中，高BNIP3表达均与较差的生存率相关。
BNIP3似乎是参与子宫内膜癌病理过程的一种重要的缺氧调节分子。鉴于高BNIP3反应性与术后不良预后相关，且与细胞毒性治疗的良好反应相关（如先前实验研究所表明），高BNIP3表达可能是I期子宫内膜癌辅助放化疗的一个指标。
