Id: 220 Clinical Significance and Co-Expression of Klk5 and Klk7 in Breast Cancer

Abstract

The family of human tissue kallikreins is a subgroup of serine proteases that has recently been identified. The family consists of 15 members, many of which exhibit an altered expression in various types of cancer, such as prostate, ovarian and breast cancer. Therefore, kallikreins may have a potential role as markers for malignancy. Human kallikrein 5 (KLK5, HSCTE) and 7 (KLK7, HSCCE) are members of the kallikrein family that have been identified from a keratinocyte library. These serine proteases are implicated in the degradation of intercellular cohesive structures in the outermost layer of the skin and contribute to the cell shedding process at the skin surface. It has been proposed that hK5 may act as activator of hK7 in the above process. KLK5 has been shown to be differentially expressed in a variety of endocrine tumors including ovarian, breast and prostate cancer. KLK7 is differentially expressed in ovarian and breast cancer and may be a potent biomarker for these diseases. The purpose of our study was to examine the possible co-expression of the two genes in breast cancer. We developed RT-PCR methods in order to selectively amplify the full length splice variants of KLK5 and KLK7. The mRNA expression of the two genes was examined in a group of 80 breast cancer samples. Actin was used as a house-keeping gene. The PCR products were sequenced in order to verify their identity. The results were correlated to other clinical and histopathological variables as well as to patient outcome. KLK5 was found to be expressed in 30/80 (37,5%) of breast cancer tissues and KLK7 in 26/80 (32,5%). KLK7 was significantly (p=0,04) more frequently expressed in samples that were positive for KLK5 expression. KLK5 expression was more frequent in tumors with low levels of estrogen receptors (p=0,04) and progesterone receptors (p=0,005). KLK7 expression was more frequent in tumors with low levels of estrogen receptors (p=0,04). KLK7 expression was also associated with shorter overall survival. Our results are in agreement with the hypothesis that there is an interplay between KLK5 and KLK7 expression. It is also suggested by the statistical analysis that KLK5 and KLK7 expression is correlated with hormone-independent, and thus, poor prognosis tumors.