Giatromanolaki Alexandra, Sivridis Efthimios, Mendrinos Savvas, Koutsopoulos Anastasios V, Koukourakis Michael I
Department of Pathology, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
Department of Pathology, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
Urol Oncol. 2014 Jan;32(1):39.e11-8. doi: 10.1016/j.urolonc.2013.04.003. Epub 2013 Jun 17.
Up-regulation of autophagy provides an important survival mechanism to normal and malignant cells residing in a hypoxic and unfavorable nutritional environment. Yet, its role in the biology of prostate cancer remains poorly understood.
In this study we investigated the expression of four major autophagy proteins, namely the microtubule-associated protein 1 light chain 3A (LC3A), LC3B, Beclin 1, and p62, together with an enzyme of anaerobic metabolism, the lactate dehydrogenase 5 (LDH5), in relation to Gleason score and extraprostatic invasion. A series of 96 prostate adenocarcinomas was examined using immunohistochemical techniques and appropriate antibodies.
The LC3A protein was expressed in the form of "stone-like" structures, and diffuse cytoplasmic staining, the LC3B reactivity was solely cytoplasmic, whereas that of p62 and LDH5 was both cytoplasmic and nuclear. A median count of 0.90 "stone-like" structures per 200 × optical field (range 0-3.6) was highly associated with a high Gleason score. Similarly, a strong cytoplasmic LC3A, LC3B, and p62 expression, when extensive (present in>50% tumor cells per section), was significantly associated with LDH5 and a high Gleason score. In addition, extensive cytoplasmic p62 expression was related with LC3A and B reactivity and also with extraprostatic invasion. Extensive Beclin-1 expression was significantly linked with extraprostatic invasion and also with p62 and LDH5 expression.
Immunohistochemical detection of autophagy proteins may potentially prove to be useful as prognostic markers and a tool for the stratification of patients in therapeutic trials targeting autophagy in prostate cancer.
自噬上调为处于缺氧及营养不利环境中的正常细胞和恶性细胞提供了一种重要的生存机制。然而，其在前列腺癌生物学中的作用仍知之甚少。
在本研究中，我们研究了四种主要自噬蛋白，即微管相关蛋白1轻链3A（LC3A）、LC3B、Beclin 1和p62的表达，以及一种无氧代谢酶乳酸脱氢酶5（LDH5）的表达，并将其与Gleason评分和前列腺外侵犯相关联。使用免疫组织化学技术和适当抗体对一系列96例前列腺腺癌进行了检测。
LC3A蛋白以“石样”结构和弥漫性细胞质染色的形式表达，LC3B反应仅存在于细胞质中，而p62和LDH5的反应既存在于细胞质中也存在于细胞核中。每200×视野中“石样”结构的中位数计数为0.90（范围0 - 3.6）与高Gleason评分高度相关。同样，当广泛表达（每切片中>50%肿瘤细胞存在）时，强烈的细胞质LC3A、LC3B和p62表达与LDH5及高Gleason评分显著相关。此外，广泛的细胞质p62表达与LC3A和B反应性相关，也与前列腺外侵犯相关。广泛的Beclin - 1表达与前列腺外侵犯以及p62和LDH5表达显著相关。
自噬蛋白的免疫组织化学检测可能被证明作为预后标志物以及在前列腺癌自噬靶向治疗试验中对患者进行分层的工具是有用的。
