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CA 125 is a well-established marker for patients diagnosed with ovarian carcinoma. It is clearly elaborated in serous cystadenocarcinomas and less likely to be expressed in mucinous tumors. It has been 20 years since CA 125 was first recognized and it is only in recent years (the past 2) that some progress has been made toward cloning the gene, providing the basis for an understanding of the functional role of this molecule in embryonic development and neoplastic transformation. It is now clear that CA 125 is a large glycoprotein which is anchored to the epithelium by a transmembrane domain and is released into the extracellular space by enzymatic cleavage. Here, we describe a further major extension to the glycosylated extracellular amino terminal domain of this molecule. These additional data in association with our previous understanding of this molecule will provide the basis for our ability to understand the physiologic function of this molecule in biologic development and pathologic transformation. Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

CA 125 has long presented problems to both clinicians and investigators because there was no definitive information on its structure and function. Here, we describe our work on cloning the CA 125 gene with the anticipation that such information will provide the basis for understanding its structure and its physiologic role in both normal and malignant tissues. The CA 125 protein core is composed of a short cytoplasmic tail, a transmembrane domain and an extraordinarily large glycosylated extracellular structure. This structure is dominated by a repeat domain composed of 156 amino acid repeat units which encompass the epitope binding sites. The molecule also includes an amino terminal domain of serine/threonine-rich sequences which would account for most of the O-glycosylation known to be present in CA 125. CA 125 is an unusually large transmembrane glycoprotein. Its release from the surface of the cell is most probably dependent on cytoplasmic phosphorylation followed by proteolytic cleavage. The extracellular domain is characterized by a large number of repeat units (probably 60+) which encompass an interactive disulfide bridged cysteine-loop and the site of OC125 and M11 binding. Sequencing the gene provides us with the ability to initiate the quest to understand the biological function of CA 125. Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine human kallikrein 8 (hK8/TADG-14) expression in epithelial ovarian tumors and to investigate the association of hK8 expression levels with patient survival. Human kallikrein 8 protein (hK8) expression was examined by immunohistochemistry in 74 ovarian adenocarcinomas and 6 normal ovaries. Results of immunostaining were correlated with clinicopathological variables and overall survival of the patients. Human kallikrein 8 gene (KLK8) mRNA expression was examined by semi-quantitative PCR in 35 ovarian tumors and 7 normal ovaries. Expression of hK8 was not detected on the surface epithelium of normal ovaries. In contrast, hK8 expression was detected in 51.4% (38/74) of carcinomas with a significantly higher detection rate of hK8 expression being observed in early stage disease compared to advanced stage disease (p=0.0192). Data analysis using the log-rank test showed hK8 expression correlated significantly with favorable patient survival (p=0.0328). Younger age (p=0.0008), early clinical stage (p<0.0001), and low histological grades of the tumors (p=0.0018) were also associated significantly with a favorable prognosis. In a multivariate model, age (p=0.0186) and clinical stage (p<0.0001) remained associated significantly with overall survival, whereas hK8 expression and histological grade lost their significance. There was significant relationship between the hK8 expression status and KLK8 mRNA expression levels (p=0.0304). Expression of hK8 is increased during the development of ovarian cancer and down-regulated during ovarian cancer progression. Expression of hK8 is a favorable prognostic marker in patients with ovarian cancer.

CA 125 is a well-established marker for patients diagnosed with ovarian carcinoma. It is clearly elaborated in serous cystadenocarcinomas and less likely to be expressed in mucinous tumors. It has been 20 years since CA 125 was first recognized and it is only in recent years (the past 2) that some progress has been made toward cloning the gene, providing the basis for an understanding of the functional role of this molecule in embryonic development and neoplastic transformation. It is now clear that CA 125 is a large glycoprotein which is anchored to the epithelium by a transmembrane domain and is released into the extracellular space by enzymatic cleavage. Here, we describe a further major extension to the glycosylated extracellular amino terminal domain of this molecule. These additional data in association with our previous understanding of this molecule will provide the basis for our ability to understand the physiologic function of this molecule in biologic development and pathologic transformation., (Copyright 2002 S. Karger AG, Basel)