FULL PAPER Pathology Expression and significance of CHIP in canine mammary gland tumors

ABSTRACT. CHIP (Carboxy terminus of Hsc70 Interacting Protein) is an E3 ubiquitin ligase that can induce ubiquitination and degradation of several oncogenic proteins. The expression of CHIP is frequently lower in human breast cancer than in normal breast tissue. However, the expression and role of CHIP in the canine mammary gland tumor (CMGT) remain unclear. We investigated the potential correlation between CHIP expression and mammary gland tumor prognosis in female dogs. CHIP expression was measured in 54 dogs by immuno-histochemistry and real-time RT-PCR. CHIP protein expression was significantly correlated with the histopathological diagnosis, outcome of disease and tumor classification. The transcriptional level of CHIP was significantly higher in normal tissues (P=0.001) and benign tumors (P=0.009) than it in malignant tumors. CHIP protein expression was significantly correlated with the transcriptional level of CHIP (P=0.0102). The log-rank test survival curves indicated that patients with low expression of CHIP had shorter overall periods of survival than those with higher CHIP protein expression (P=0.050). Our data suggest that CHIP may play an important role in the formation and development of CMGTs and serve as a valuable prognostic marker and potential target for genetic therapy. KEY WORDS: canine mammary gland tumor, CHIP, immunohistochemistry, prognosis, RT-PCR doi: 10.1292/jvms.14-0484; J. Vet. Med. Sci. 77(11): 1465–1471, 2015 Mammary gland tumors are the most common tumors in female dogs and women [3, 31, 33]. Approximately half of all canine mammary gland tumors are malignant [5, 6]