There are several reports in the literature which suggest important functions of HE-4: over-expression in ovarian carcinoma, over-expression in prostate cancer model mice with PTEN inactivation, interaction with pleiotrophin (PTN) which regulates angiogenesis and is involved in tumor formation as well as the upregulation of HE-4 during the expected window of receptivity in the endometrium under the control of progesterone in primates [20], [30]–[32]. Here, PTEN is linked to Familial prostate cancer.