Pang Tony, Kaufman Antony, Choi Julian, Gill Anthony, Drummond Martin, Hugh Thomas, Samra Jaswinder
Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital ; Northern Clinical School, University of Sydney.
Department of Anatomical Pathology, Royal North Shore Hospital.
Mol Clin Oncol. 2015 Mar;3(2):308-316. doi: 10.3892/mco.2014.482. Epub 2014 Dec 30.
Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors involved in lipid metabolism and liver response to injury. We hypothesised that differences in the expression of PPARs may reflect differences in the cellular microenvironment of the liver and, consequently, in the behaviour of colorectal liver metastases. Of the 145 patients who underwent hepatectomy for colorectal liver metastases between 1998 and 2007, 103 had adequate tissue for PPAR staining and histological re-evaluation. The histological characteristics evaluated included sinusoidal dilatation, perisinusoidal fibrosis, ballooning and steatosis. PPAR- α and-γ staining was performed and the results were correlated with clinical and survival data. Lobular inflammation and sinusoidal dilatation were the most common histopathological abnormalities. A total of 50% of the patients were PPAR- α-negative and 34% were PPAR- γ-negative. More patients exhibited lobular inflammation in the PPAR- α -positive group (P=0.023) compared to patients with negative PPAR- α staining, as seen on the multivariate analysis. PPAR- γpositivity was associated with oxaliplatin use, surgical margins ≥1 mm and a trend towards a lesser degree of fibrosis. The median follow-up in this cohort of patients was 48 months. Patients with PPAR- α staining had a worse overall survival (median, 36 vs. 79 months, P=0.037) compared to those with no PPAR- α staining. There was no correlation between PPAR- α or-γpositivity and disease-free survival. In conclusion, PPAR- α staining is associated with lobular inflammation and worse overall survival in patients with colorectal liver metastases. The exact mechanism underlying this finding remains unclear and further research into the diagnostic and therapeutic implications is required.
过氧化物酶体增殖物激活受体（PPARs）是一类参与脂质代谢和肝脏对损伤反应的核受体。我们推测，PPARs表达的差异可能反映肝脏细胞微环境的差异，进而反映结直肠癌肝转移的行为。在1998年至2007年间接受结直肠癌肝转移肝切除术的145例患者中，103例有足够的组织用于PPAR染色和组织学重新评估。评估的组织学特征包括肝血窦扩张、肝血窦周围纤维化、气球样变和脂肪变性。进行了PPAR-α和-γ染色，并将结果与临床和生存数据相关联。小叶炎症和肝血窦扩张是最常见的组织病理学异常。共有50%的患者PPAR-α阴性，34%的患者PPAR-γ阴性。与PPAR-α染色阴性的患者相比，PPAR-α阳性组中更多患者出现小叶炎症（P=0.023），多因素分析显示如此。PPAR-γ阳性与使用奥沙利铂、手术切缘≥1mm以及纤维化程度较轻的趋势相关。该队列患者的中位随访时间为48个月。与无PPAR-α染色的患者相比，PPAR-α染色的患者总生存期更差（中位生存期分别为36个月和79个月，P=0.037）。PPAR-α或-γ阳性与无病生存期之间无相关性。总之，PPAR-α染色与结直肠癌肝转移患者的小叶炎症和更差的总生存期相关。这一发现的具体机制尚不清楚，需要进一步研究其诊断和治疗意义。
