lewis-x-antigen and Choriocarcinoma

Trophoblast cell adhesion and migration are carefully coordinated during normal placental development. We have compared the expression of three adhesion molecules, E-cadherin, β-catenin, and Lewis x, by immunohistochemistry during normal trophoblast differentiation, and in hydatidiform moles and choriocarcinomas. Both E-cadherin and β-catenin were expressed in normal placenta cytotrophoblast, and this expression decreased with trophoblast maturation. E-cadherin was mainly localized along the contact between cytotrophoblast and syncytiotrophoblast, which indicates its role in the differentiation of the syncytial layer. Lewis x disappeared progressively during differentiation of normal villous vessels, and was expressed in molar pregnancies. Interestingly, whereas choriocarcinomas were not, or poorly, stained, invasive hydatidiform moles (invHMs) strongly expressed Lewis x in vascular structures. This observation correlated well with E-cadherin and β-catenin expression and suggests that these three markers are associated with the invasive transformation. The presence of robust endothelial structures in invHMs could also explain their ability to maintain organized villous architecture (contrary to metastatic choriocarcinomas) during their invasion of extrauterine tissues such as the lung or the brain after dissemination through the blood flow. In our hands, Lewis x appeared to be a new, reliable marker that can be used to clearly distinguish invHMs from choriocarcinomas.

Topics: Abnormal Karyotype; Adult; beta Catenin; Cadherins; Choriocarcinoma; Diagnosis, Differential; Female; Gestational Age; Humans; Hydatidiform Mole, Invasive; In Situ Hybridization, Fluorescence; Lewis X Antigen; Pregnancy; Trophoblasts; Uterine Neoplasms

Stage-Specific Embryonic Antigen-1 (SSEA-1), originally discovered on mouse teratocarcinomas, has since been found on some human non-seminomatous germ-cell tumors and adenocarcinomas, as well as on some adult mouse and human tissues. A monoclonal antibody to this antigen (anti-SSEA-1; IgM, kappa) was used for radioimmunolocation. Nude mice bearing the human choriocarcinoma BeWo, which is SSEA-1 positive, were injected using a mixture of [131I]anti-SSEA-1 and [125I]MOPC 104E, an unselected myeloma protein of the same heavy-chain isotype. Animals were sacrificed at 24 hour intervals; the radioactive deposition due to both antibodies was determined for both tumors and normal organs. Accumulation of anti-SSEA-1 in the tumor was consistantly rapid and specific, while little accumulation of the unselected myeloma protein occurred. At five days after injection, an average of 3% of the initial dose of specific antibody was retained per gram of tumor; the tumor/blood ratio was 11, tumor/muscle was 80. Gamma-camera imaging allowed ready location of the tumors. Tumors could also be imaged using F(ab')2 antibody fragments.

Topics: Animals; Antibodies, Monoclonal; Antigen-Antibody Complex; Choriocarcinoma; Female; Glycolipids; Humans; Iodine Radioisotopes; Lewis X Antigen; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Pregnancy; Radionuclide Imaging; Transplantation, Heterologous; Uterine Neoplasms

Both murine and heterotransplanted human nonseminomatous germ-cell tumors have been successfully located by external scintigraphy using radioiodinated anti-SSEA-1, a monoclonal IgM, and its pepsin-derived antigen-binding fragment, F(ab')2 mu. Antibody localization in the tumor is mainly due to antigenic specificity, rather than to nonspecific trapping, and depends strongly on the amount of time after injection. The antibody has been used for drug targeting in vitro and in vivo.

Topics: Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Antineoplastic Agents; Choriocarcinoma; Female; Glycolipids; Humans; Immunoglobulin Fab Fragments; Iodine Radioisotopes; Lewis X Antigen; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; Pregnancy; Radionuclide Imaging; Teratoma; Transplantation, Heterologous

Murine stage-specific embryonic antigens (SSEA-1, SSEA-3) are well characterized oncofetal antigens and have been identified in several human tumors. The current study was undertaken to determine the localization of SSEA-1 and SSEA-3 in hydatidiform mole, normal human placenta, and gestational choriocarcinoma. SSEA-3 did not react with any cellular components in hydatidiform moles, normal placentas, or choriocarcinoma cell lines. SSEA-1 was detectable in two human gestational choriocarcinoma cell lines, but not in the trophoblastic cells of 10 hydatidiform moles or in nine normal placentas between 6 weeks and term gestation. Therefore, according to this oncofetal marker system, the trophoblast in hydatidiform mole is more like normal trophoblast than gestational choriocarcinoma.

Topics: Antigens, Neoplasm; Cell Line; Choriocarcinoma; Female; Fluorescent Antibody Technique; Gestational Age; Glycolipids; Histocytochemistry; Humans; Hydatidiform Mole; Immunoenzyme Techniques; Lewis X Antigen; Lymph Nodes; Neoplasm Staging; Placenta; Pregnancy; Risk; Trophoblastic Neoplasms; Trophoblasts; Uterine Neoplasms