Expression of PPARδ in multistage carcinogenesis of the colorectum:: implications of malignant cancer morphology

Whether peroxisome proliferator-activated receptor (PPAR) delta is a good target for the chemoprevention and/or treatment of colorectal cancer (CRC) remains controversial. Our goal was to examine PPAR delta expression in multistage carcinogenesis of the colorectum and to assess the relevance of PPAR delta in CRC. Immunohistochemical analysis indicated that PPAR delta expression increased from normal mucosa to adenomatous polyps to CRC. In cancer tissues, the PPAR delta protein was accumulated only in those cancer cells with highly malignant morphology, as represented by a large-sized nucleus, round-shaped nucleus, and presence of clear nucleoli. Interestingly, the cancer tissue often contained both PPAR delta- positive and -negative areas, each retaining their respective specific morphological features. Moreover, this pattern persisted even when PPAR delta- positive and -negative cells were aligned next to each other within a single cancer nest or gland and was present in the majority of CRC cases. Immunohistochemistry for Ki-67 proliferation marker showed no significant correlation between Ki-67 and PPAR delta in CRC samples. Based on Western blot analysis and quantitative RT-PCR, high PPAR delta protein expression correlated with high PPAR delta mRNA levels. Peroxisome proliferator-activated receptor d may have a supporting role in tumorigenesis, and the close association between PPAR delta expression and malignant morphology of CRC cells suggests a pivotal role in cancer tissue.