Expressed at low levels in benign AbMole Nodakenin ovarian tumors. Based on these patterns, HE4 can be clearly utilized as a marker for the early diagnosis of ovarian cancer and assessment of therapeutic effects. Drapkin et al. reported that culture medium from ovarian carcinoma cells contains a secreted form of HE4 that is Nglycosylated with an approximate molecular weight of 25 kDa. However, several issues, such as whether highly expressed HE4 in serum is in the glycosylated form, its structure and mechanisms of action, are yet to be clarified. Drapkin and colleagues reported the presence of HE4 in both the endoplasmic reticulum and Golgi apparatus of ovarian carcinoma cells. It is proposed that HE4 is glycosylated in endoplasmic reticulum and Golgi apparatus of ovarian carcinoma cells and then secreted into culture medium, based on the molecular weights of the protein before and after treatment with the deglycosylation enzyme, N-glycosidase F. Consistent with this theory, we showed that HE4 in culture medium from ovarian carcinoma cells is in the glycosylated form. Moreover, the molecular weight of HE4 in culture medium coincided with those in ovarian cancer tissues and cells, signifying that HE4 is already modified by glycosyl residues. A logical prediction from our studies is that HE4 is glycosylated in the blood of patients with ovarian carcinoma. Our results show for the first time that HE4 is present in ovarian cancer, and benign tumor tissues, ovarian carcinoma cells, and culture medium contain Lewis y antigen. Moreover, expression of the Lewis y antigen component of HE4 from ovarian cancer was higher than that from benign tumor. Our data indicate that the glycoprotein, HE4, possibly exists as two protein isoforms expressed at equivalent levels. However, expression in ovarian cancer cells was lower and the tendency is not equal. This may be attributable to the content and structure of HE4 in tissues. In 2002, analysis of the HE4 gene revealed that at least five putative protein isoforms can be generated via complex alternative splicing. Tokuishi et al. illustrated that expression of the splice variant, HE4-V3, is associated with favorable prognosis in pulmonary adenocarcinoma. Based on the different gene products identified, we proposed the existence of three types of proteins with different molecular weights. However, only two possible proteins containing Lewis y antigen were identified in this study. It is currently unclear whether other isoforms also exist in ovarian cancer or whether these proteins are present in the glycosylated form at the same time. Moreover, we are yet to establish whether the fucosylated form affects the occurrence, development or migration of ovarian cancer. Among the tissue specimens examined in our study, positive expression rates of HE4 in malignant and boundary ovarian tissues were significantly higher than those in benign tumor, similar to Lewis y antigen levels in ovarian cancer.