Karihtala Peeter, Mäntyniemi Anne, Kang Sang Won, Kinnula Vuokko L, Soini Ylermi
Department of Pathology, University of Oulu and Oulu University Hospital, 90014 Oulu, Finland.
Clin Cancer Res. 2003 Aug 15;9(9):3418-24.
Peroxiredoxins (Prxs) are a novel group of peroxidases containing high antioxidant efficiency and some of them having also effects on cell differentiation and apoptosis. The mammalian Prx family has six distinct members located in various subcellular locations, including peroxisomes and mitochondria, places where oxidative stress is most evident.
We examined immunohistochemically a large set of samples from patients with breast carcinoma and investigated associations with parameters such as tumor-node-metastasis classification, hormone receptor status, and patient survival. Three biopsies of healthy breast tissue were used as controls.
Expression of peroxiredoxins I, III, IV, and V was found in >or=80% of cases, whereas the expression of Prx II and VI was less frequent. Increased expression of Prx III was found to associate with the presence of progesterone (P = 0.02) and estrogen (P = 0.03) receptors, and Prxs IV (P = 0.009) and VI (P = 0.04) were overexpressed in progesterone receptor positive cases. Prx V was the only isoform that associated with items of tumor-node-metastasis classification, it was connected to a larger tumor size (P = 0.05) and positive lymph node status (P = 0.04). Prx V positivity was also connected with shorter survival (P = 0.04), whereas Prxs III (P = 0.002) and IV (P = 0.02) were related to better prognosis, probably resulting from their connection with a positive hormone receptor status.
In conclusion, we found that expression of peroxiredoxins, especially III, IV and V, is increased in breast malignancy, suggesting the induction of Prxs as response to increased production of reactive oxygen species in carcinomatous tissue.
过氧化物还原酶(Prxs)是一类新型的过氧化物酶,具有高抗氧化效率,其中一些还对细胞分化和凋亡有影响。哺乳动物Prx家族有六个不同成员,位于包括过氧化物酶体和线粒体等不同亚细胞位置,这些地方氧化应激最为明显。
我们对大量乳腺癌患者样本进行免疫组织化学检查,并研究其与肿瘤-淋巴结-转移分类、激素受体状态和患者生存等参数的相关性。取三份健康乳腺组织活检样本作为对照。
在≥80%的病例中发现过氧化物还原酶I、III、IV和V有表达,而过氧化物还原酶II和VI的表达频率较低。发现过氧化物还原酶III表达增加与孕激素(P = 0.02)和雌激素(P = 0.03)受体的存在相关,过氧化物还原酶IV(P = 0.009)和VI(P = 0.04)在孕激素受体阳性病例中过表达。过氧化物还原酶V是唯一与肿瘤-淋巴结-转移分类项目相关的亚型,它与更大的肿瘤大小(P = 0.05)和阳性淋巴结状态(P = 0.04)有关。过氧化物还原酶V阳性也与较短的生存期相关(P = 0.04),而过氧化物还原酶III(P = 0.002)和IV(P = 0.02)与较好的预后相关,这可能是由于它们与阳性激素受体状态有关。
总之,我们发现过氧化物还原酶,尤其是III、IV和V,在乳腺恶性肿瘤中表达增加,提示过氧化物还原酶的诱导是对癌组织中活性氧产生增加的反应。