Lee Banghyun, Lee Hee Jin, Cho Hye-Yon, Suh Dong Hoon, Kim Kidong, No Jae Hong, Kim Haeryoung, Kim Yong-Beom
Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi-do, Republic of Korea.
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul-si, Republic of Korea.
Anticancer Res. 2015 Jul;35(7):3909-16.
BACKGROUND/AIM: The expression patterns of the key DNA damage response-related proteins, ataxia-telangiectasia and tfiih/ner complex atp-dependent 5'-3' dna helicase subunit rad3 (RAD3)-related (ATR) and ataxia-telangiectasia-mutated (ATM) proteins in ovarian cancer are not well-known. This study aimed to evaluate the expressions of ATR and ATM proteins, and to investigate their clinical significance in epithelial ovarian carcinoma (EOC).
The expressions of nuclear/cytoplasmic Ser428-phosphorylated ATR (p-ATR) and Ser1981-phosphorylated ATM (p-ATM) were evaluated by immunohistochemistry in 100 patients with EOC. The clinical significances of p-ATR and p-ATM protein expression were evaluated in terms of tumor progression and survival.
Low expression of cytoplasmic p-ATR was significantly associated with advanced stage, serous histology, large residual mass, and high preoperative serum CA125 level. Univariate survival analysis revealed that low expression of cytoplasmic p-ATR protein was significantly associated with poor disease-free survival and poor overall survival.
Our study demonstrates that cytoplasmic ATR protein might serve as a prognostic biomarker for patients with EOC.
背景/目的:共济失调毛细血管扩张症和TFIIH/NER复合物ATP依赖性5'-3' DNA解旋酶亚基RAD3相关蛋白(ATR)以及共济失调毛细血管扩张症突变蛋白(ATM)等关键DNA损伤反应相关蛋白在卵巢癌中的表达模式尚不明确。本研究旨在评估ATR和ATM蛋白的表达情况,并探讨它们在上皮性卵巢癌(EOC)中的临床意义。
采用免疫组织化学方法评估100例EOC患者细胞核/细胞质中Ser428磷酸化的ATR(p-ATR)和Ser1981磷酸化的ATM(p-ATM)的表达。从肿瘤进展和生存方面评估p-ATR和p-ATM蛋白表达的临床意义。
细胞质p-ATR低表达与晚期、浆液性组织学、大残留肿块以及术前血清CA125水平高显著相关。单因素生存分析显示,细胞质p-ATR蛋白低表达与无病生存期差和总生存期差显著相关。
我们的研究表明,细胞质ATR蛋白可能作为EOC患者的预后生物标志物。