Carsten F J Bakhuis, Paul J van Diest, Britt B M Suelmann, Natalie D Ter Hoeve, Sven van Kempen, Pieter J Westenend, Sabine C Linn, Elsken van der Wall, Carmen van Dooijeweert
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引用次数: 0
Abstract
Aims: Breast cancer (BC) during pregnancy (PrBC) and the postpartum period (PPBC) often exhibits more aggressive tumour characteristics and is associated with a poorer prognosis compared with age-matched nonpregnant patients with BC. The underlying mechanisms for this increased aggressiveness remain unresolved. Intratumoral hypoxia, a known adverse prognostic marker in nonpregnant BC, has not yet been studied in PrBC/PPBC. This is particularly intriguing due to the potential exposure to angiogenesis-stimulating factors during pregnancy, which may influence tumour behaviour.
Methods: Tumour tissues from 148 patients with PrBC and 45 patients with PPBC were used to create a tissue microarray (TMA), and clinical and outcome data were obtained. The TMAs were stained for hypoxia-associated protein markers: glucose transporter-1, carbonic anhydrase IX and hypoxia-inducible factor-1α.
Results: Of all 193 tumours, 152 (79%) expressed at least one of these proteins indicative of intratumoral hypoxia. The presence of intratumoral hypoxia was associated with a higher histological grade (83% grade III vs 63%) and frequent hormone receptor negativity (68% vs 39%). In a multivariable analysis, the presence of intratumoral hypoxia indicated a significantly worse prognosis (HR 2.532, 95% CI 1.1 to 5.7) for patients with PrBC and PPBC.
Conclusion: This unique study, the first in patients with PrBC and PPBC, showed that, despite their likely exposure to angiogenesis-stimulating factors, intratumoral hypoxia is frequent and affects 79% of patients. Importantly, patients with tumours overexpressing hypoxia markers have significantly worse survival. This suggests that hypoxia may be an important mechanism in carcinogenesis and clinical behaviour of PrBC and PPBC.
目的:与年龄匹配的非妊娠乳腺癌患者相比,妊娠期(PrBC)和产后(PPBC)乳腺癌(BC)通常表现出更具侵袭性的肿瘤特征,且预后较差。这种侵略性增强的潜在机制仍未得到解决。肿瘤内缺氧是已知的非妊娠BC的不良预后标志物,但尚未在PrBC/PPBC中进行研究。这是特别有趣的,因为在怀孕期间可能暴露于血管生成刺激因素,这可能会影响肿瘤的行为。方法:利用148例PrBC患者和45例PPBC患者的肿瘤组织构建组织微阵列(TMA),获取临床和预后数据。对tma进行缺氧相关蛋白标记:葡萄糖转运蛋白-1、碳酸酐酶IX和缺氧诱导因子-1α染色。结果:在所有193个肿瘤中,152个(79%)表达至少一种这些蛋白,表明肿瘤内缺氧。肿瘤内缺氧的存在与较高的组织学分级(III级83%对63%)和频繁的激素受体阴性(68%对39%)相关。在一项多变量分析中,对于PrBC和PPBC患者,肿瘤内缺氧的存在表明预后明显较差(HR 2.532, 95% CI 1.1至5.7)。结论:这项独特的研究,首次在PrBC和PPBC患者中进行,表明尽管他们可能暴露于血管生成刺激因子,但肿瘤内缺氧是常见的,并影响了79%的患者。重要的是,肿瘤过表达缺氧标志物的患者生存率明显较差。这提示缺氧可能是PrBC和PPBC的癌变和临床行为的重要机制。
期刊介绍:
Journal of Clinical Pathology is a leading international journal covering all aspects of pathology. Diagnostic and research areas covered include histopathology, virology, haematology, microbiology, cytopathology, chemical pathology, molecular pathology, forensic pathology, dermatopathology, neuropathology and immunopathology. Each issue contains Reviews, Original articles, Short reports, Correspondence and more.