Abstract
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.