PDF(Pubmed)
Abstract：
Among autophagic-related proteins, p62/SQSTM1/Sequestosome-1 represents a relevant actor in cellular proliferation and neoplastic growth. Although, recently, p62 expression has been analyzed in different neurodegenerative and glial neoplastic diseases, no available information have been reported in meningiomas, which have an high epidemiological relevance being the second most common category of intracranial tumors after gliomas. Generally meningiomas have a benign behavior, but their recurrence is not uncommon mainly when atypical or anaplastic varieties occur. However, intranuclear vacuoles have been ultrastructurally observed in meningiomas, and they were labelled by p62 antibodies. Therefore, in the present study, we have investigated p62 immunohistochemical pattern in a cohort of 133 cases representative of low- and high-grade meningiomas, to verify if p62 expression may be related to clinicopathological data, thus achieving a potential prognostic role. The p62 immunoexpression was frequently found in the nucleus and cytoplasm of neoplastic elements, and utilizing an intensity-distribution score, 55 (41.3%) cases were considered as high expressors while 78 (58.7%) cases were instead recorded as low expressors. Fifteen cases exhibited recurrences of the disease, 14 of which were codified as high expressors. Moreover, a direct relationship between p62 and Mib-1 immunoexpression as well as between p62 and neoplastic grade have been documented. Finally, we suggest that impaired autophagic flux with an increase in p62 expression may be involved in the activation of NRF2 also contributing in the development of recurrence in meningioma patients.
摘要：
在自噬相关蛋白中，p62/SQSTM1/Sequestosome-1代表细胞增殖和肿瘤生长中的相关因子。虽然,最近,p62在不同的神经退行性疾病和神经胶质肿瘤疾病中的表达，没有脑膜瘤的可用信息报道，具有高度流行病学相关性，是仅次于神经胶质瘤的第二大常见颅内肿瘤。一般来说脑膜瘤有良性行为，但它们的复发并不少见，主要是在发生非典型或间变性变种时。然而,在脑膜瘤中超微结构观察到核内液泡，它们被p62抗体标记。因此,在本研究中，我们研究了一组133例代表低度和高度脑膜瘤的p62免疫组织化学模式，为了验证p62表达是否可能与临床病理数据有关，从而实现潜在的预后作用。p62免疫表达常在肿瘤元件的细胞核和细胞质中发现，利用强度分布分数，55例（41.3％）被认为是高表达者，而78例（58.7％）被记录为低表达者。15例表现出疾病复发，其中14个被编码为高表达者。此外，已经记录了p62和Mib-1免疫表达之间以及p62和肿瘤级别之间的直接关系。最后,我们提示,在脑膜瘤患者中,随着p62表达的增加,自噬通量受损可能与NRF2的激活有关,也可能导致复发.
