Giatromanolaki Alexandra, Koukourakis Michael I, Georgiou Ioannis, Kouroupi Maria, Sivridis Efthimios
Department of Pathology, Democritus University of Thrace and University General Hospital of Alexandroupolis, Alexandroupolis, Greece
Department of Radiotherapy/Oncology, Democritus University of Thrace and University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
Anticancer Res. 2018 Dec;38(12):6827-6833. doi: 10.21873/anticanres.13056.
The current study examined the key proteins involved in autophagosome formation and their prognostic role in gastric cancer.
Paraffin-embedded tissues from 121 consecutive patients treated with surgery for gastric cancer were analyzed immunohistochemically for the expression of autophagic proteins microtubule-associated proteins 1A/1B light chain 3A and 3B (LC3A, LC3B) and beclin-1 (encoded by BECN1 gene). Assessment of proliferative index using the MIB1 monoclonal antibody (recognizing an epitope of the Ki-67 antigen, encoded by the MK167 gene) and correlations with histopathological [corrected].
Strong cytoplasmic expression was noted for all studied proteins, although to a varying proportion, the median percentage being 30% for LC3A, and 40% for LC3B and beclin-1. The median score of LC3A stone-like structures (SLS) was 0.2 (range 0-1) and the median proliferative index was 30% (range=0-95%). A significant association between LC3A, LC3B and beclin-1 expression was confirmed (p<0.01). SLS score was higher in tumors of the gastro-esophageal junction (p=0.009), and beclin-1 was overexpressed in intestinal-type tumors (p=0.001). High SLS score (p=0.008) was significantly related to poor prognosis, and this finding persisted in multivariate analysis (hazard ratio(HR)=2.01, p=0.003).
Intense autophagic activity, as assessed by LC3A immunostaining and SLS quantification, is a strong prognostic marker in gastric cancer and can be useful for clinical application.
本研究检测了参与自噬体形成的关键蛋白及其在胃癌中的预后作用。
对121例连续接受胃癌手术治疗患者的石蜡包埋组织进行免疫组织化学分析，检测自噬蛋白微管相关蛋白1A/1B轻链3A和3B（LC3A、LC3B）以及Beclin-1（由BECN1基因编码）的表达。使用MIB1单克隆抗体（识别由MK167基因编码的Ki-67抗原的一个表位）评估增殖指数，并与组织病理学[校正后]进行相关性分析。
所有研究蛋白均可见强细胞质表达，尽管比例不同，LC3A的中位数百分比为30%，LC3B和Beclin-1为40%。LC3A结石样结构（SLS）的中位数评分是0.2（范围0-1），增殖指数中位数为30%（范围=0-95%）。LC3A、LC3B和Beclin-1表达之间存在显著相关性（p<0.01）。胃食管交界部肿瘤的SLS评分更高（p=0.009），Beclin-1在肠型肿瘤中过表达（p=0.001）。高SLS评分（p=0.008）与预后不良显著相关，这一发现经多因素分析后仍然存在（风险比（HR）=2.01，p=0.003）。
通过LC3A免疫染色和SLS定量评估的强烈自噬活性是胃癌的一个强有力的预后标志物，可用于临床应用。
