lewis-x-antigen and Uterine-Neoplasms

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

Mesonephric (wolffian) neoplasms of the female genital tract are infrequent and found in sites where embryonic remnants of wolffian origin are usually detected, such as the uterine cervix, broad ligament, mesosalpinx, and ovary. Their diagnosis is difficult because of the absence of specific immunohistochemical markers for mesonephric derivatives. We present the first report of adenocarcinoma of mesonephric type arising as a purely myometrial mass without endometrial or cervical involvement in the uterine corpus of a 33-year-old woman. The tumor showed a combination of patterns, with retiform areas, ductal foci, and small tubules with eosinophilic secretion, which merged with solid sheets of cells with a sarcomatoid appearance. Immunohistochemically, neoplastic cells were diffusely positive for cytokeratin 7, epithelial membrane antigen, and CD15 and focally positive for BerEP4 and vimentin. A hitherto unreported feature was the positivity for CD10 in neoplastic cells, which was also present in a large number of control tissues obtained from male mesonephric derivatives and female mesonephric remnants and tumors. Furthermore, CD10 was negative in controls from müllerian epithelia of the female genital tract and in their corresponding tumors. Therefore, the expression of CD10 by mesonephric remnants may be useful in establishing the diagnosis of tumors with mesonephric differentiation.

Topics: Adenocarcinoma; Adult; Antigens, Neoplasm; Antigens, Surface; Biomarkers, Tumor; Cell Differentiation; Female; Humans; Hysterectomy; Immunohistochemistry; Keratin-7; Keratins; Lewis X Antigen; Mesonephroma; Mesonephros; Mucin-1; Neprilysin; Radiotherapy, Adjuvant; Treatment Outcome; Uterine Neoplasms; Vimentin

Uterine adenomatoid tumors (UATs) may be difficult to distinguish from metastatic adenocarcinoma, particularly in pelviscopic biopsy specimens, myomectomy specimens, or endometrial samplings. This problem may arise because of the infiltration of vacuolated mesothelial cells between fascicles of prominent smooth muscle, which is a characteristic feature in UAT. This diagnostic difficulty has led to inappropriate surgery as reported in the past. Eleven UATs were studied to clarify the differences between these tumors and metastatic adenocarcinoma. Six of the tumors were grossly indistinguishable from leiomyomas. Histologically, the neoplastic mesothelial cells diffusely infiltrated smooth muscle fascicles in all cases, mimicking the pattern of metastatic adenocarcinoma. Immunohistochemical studies using antikeratin and Ber-EP4 antibodies were positive in the mesothelial component in all 11 and nine tumors, respectively, whereas all 11 UATs were negative using antibodies to carcinoembryonic antigen, CD15, TAG-72, and epithelial membrane antigen. Immunoreactivity using Ber-EP4 was focal, membranous, and usually weak, although a strong signal was present in one case. Immunoreactivity using Ber-EP4 (compared with negativity reported for mesothelial proliferations of other sites) may be related to the unique müllerian characteristic of the female peritoneum. Although nonimmunoreactivity for Ber-EP4 favors a diagnosis of UAT over that of adenocarcinoma, Ber-EP4 immunoreactivity does not exclude UAT.

Topics: Adenocarcinoma; Adenomatoid Tumor; Adult; Aged; Antibodies, Monoclonal; Antigens, Differentiation; Antigens, Neoplasm; Biopsy; Carcinoembryonic Antigen; Cell Division; Diagnosis, Differential; Female; Glycoproteins; Humans; Immunohistochemistry; Lewis X Antigen; Middle Aged; Uterine Neoplasms

The efficacy of sialyl SSEA-1 antigen (SLX), a tumor-associated carbohydrate antigen, as a test for gynecological cancer was investigated. The test was found to be positive in 64.5% of all patients with ovarian cancers; this rate is lower than that obtained with CA 125. On the other hand, relatively few false-positive results were observed. Tests were false-positive in 25.0% of patients with endometrial cysts; 25.0% of women in the first trimester of pregnancy and 0.0% of menstruating woman had false-positive results. These percentages were lower than those for CA 125. It is concluded that SLX is a tumor marker with inferior sensitivity and high specificity, compared with CA 125. Since positive tests with SLX in patients with ovarian cancer mostly overlapped the positive tests for CA 125, the usefulness of a combination assay was considered to be low. The SLX test was positive in 18.6 and 25.0% of patients with cervical cancer and endometrial cancer, respectively, and it was concluded that SLX is useless as a serum tumor marker for uterine cancer.

Topics: Antigens, Tumor-Associated, Carbohydrate; Carcinoma; Cysts; Female; Glycolipids; Humans; Lewis X Antigen; Menstruation; Ovarian Neoplasms; Pregnancy; Pregnancy Trimester, First; Sialoglycoproteins; Uterine Neoplasms

Sialyl SSEA-1 antigen (SLX) is a highly specific tumor marker composed of sugar chain antigens that have Lewis X at their terminals and bind to sialic acid. This antigen is rarely detected in normal tissues, and is present in adenocarcinoma and fetal tissues. We studied the clinical usefulness of SLX in gynecological patients and obtained the following results. (1) The antigen was frequently positive in patients with ovarian cancer with a mean of 89.5 +/- 48.3 U/ml (72.8%, 8/11) and in those with endometriosis with a mean of 39.8 +/- 10.3 U/ml (75.0%, 6/8). (2) Among the gynecological malignancies, the percent positivity was low in those with cervical cancer (20.0%, 5/25), endometrial cancer (33.3%, 1/3), and cancer of the fallopian tube (33.3%, 1/3). (3) The antigen was negative in 20 with myoma uteri, 20 normal pregnant women, and 9 nonpregnant healthy women during the follicular, luteal, or menstrual phase. It was negative in 8 of 9 patients with benign ovarian cyst. False negative results were rare. (4) The SLX level was higher in the ascites than in the serum in patients with ovarian cancer and in those with benign ovarian tumors. (5) The serum SLX in patients with ovarian cancer, which was positive before tumor resection, became negative 2 weeks postoperatively. These results suggest that SLX is a tumor marker with a high specificity to adenocarcinoma of the reproductive organs.

Topics: Adenocarcinoma; Adult; Antigens, Neoplasm; Biomarkers, Tumor; Endometriosis; False Positive Reactions; Female; Genital Diseases, Female; Genital Neoplasms, Female; Glycolipids; Humans; Lewis X Antigen; Menstrual Cycle; Middle Aged; Myoma; Ovarian Neoplasms; Pregnancy; Uterine Cervical Neoplasms; 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

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