Department of Pathology, Chi-Mei Foundational Medical Center, Tainan, Taiwan.
J Clin Pathol. 2012 Apr;65(4):309-14. doi: 10.1136/jclinpath-2011-200489. Epub 2012 Jan 21.
Increased β-oxidation of branched-chain fatty acids provides an additional metabolic advantage for cancer cells thereby enhancing tumour development and progression. Alpha-methylacyl coenzyme A racemase (AMACR) is an enzyme essential for the catabolism of branched-chain fatty acids that allows their subsequent β-oxidation and thus plays an important role in generating biological energy. However, the expression of AMACR has never been systemically investigated in gallbladder carcinoma. This study evaluated the expression status, associations with clinicopathological variables and prognostic implications of AMACR in a well-defined cohort of gallbladder carcinoma and confirmed their expression status in gallbladder carcinoma cells.
AMACR immunostaining was assessable in 89 cases on tissue microarrays of gallbladder carcinoma, and it was correlated with clinicopathological factors and patient survival. In three gallbladder carcinoma cell lines and one non-tumorigenic cholangiocyte, AMACR mRNA expression was measured by real-time reverse transcription PCR and the endogenous expression of AMACR protein was analysed by western blotting.
AMACR overexpression was significantly associated with an advanced primary tumour status (p=0.027) and American Joint Committee on Cancer stage (p=0.027), an increased histological grade (p=0.002) and vascular invasion (p=0.017). Importantly, AMACR overexpression independently predicted worse disease-specific survival (p=0.0452, RR 1.887). Expression levels of AMACR mRNA and total protein in various cells were comparable. The abundance of AMACR expression increased in tumour cells and was even higher in the metastatic cell line.
In primary gallbladder carcinoma, AMACR overexpression was correlated with important prognosticators and independently portended worse outcomes, highlighting the potential prognostic and therapeutic utility of AMACR in gallbladder carcinoma.
支链脂肪酸的β氧化增加为癌细胞提供了额外的代谢优势，从而促进肿瘤的发展和进展。α-甲基酰基辅酶 A 消旋酶（AMACR）是分解支链脂肪酸所必需的酶，允许它们随后进行β氧化，因此在产生生物能量方面发挥着重要作用。然而，AMACR 在胆囊癌中的表达从未被系统研究过。本研究评估了 AMACR 在明确定义的胆囊癌队列中的表达状态、与临床病理变量的关联及其对患者生存的预后意义，并在胆囊癌细胞中证实了其表达状态。
在胆囊癌组织微阵列上可评估 89 例病例的 AMACR 免疫染色，并将其与临床病理因素和患者生存相关联。在三种胆囊癌细胞系和一种非致瘤性胆管细胞中，通过实时逆转录 PCR 测量 AMACR mRNA 表达，并通过 Western blot 分析 AMACR 内源性表达。
AMACR 过表达与原发性肿瘤进展（p=0.027）和美国癌症联合委员会分期（p=0.027）、组织学分级升高（p=0.002）和血管侵犯（p=0.017）显著相关。重要的是，AMACR 过表达独立预测疾病特异性生存较差（p=0.0452，RR 1.887）。各种细胞中 AMACR mRNA 和总蛋白的表达水平相当。肿瘤细胞中 AMACR 表达的丰度增加，在转移性细胞系中甚至更高。
在原发性胆囊癌中，AMACR 过表达与重要的预后指标相关，并独立预示着较差的结局，突出了 AMACR 在胆囊癌中的潜在预后和治疗效用。
