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Expression of oncofetal antigens in normal human placenta, complete hydatidiform mole, and gestational choriocarcinoma
262
SOCIETY OF GYNECOLOGIC
ONCOLOGISTS-ABSTRACTS
39. Expression of Oncofetal Antigens in Normal Human Placenta, Complete Hydatidiform Mole, and Gestational Choriocarcinoma. D. J. ANDERSON, R. S. BERKOWITZ, D. P. GOLDSTEIN, AND R. KNAPP, New England Trophoblastic Disease Center, Departments of Pathology and Obstetrics and Gynecology, Harvard Medical School. Boston, Massachusetts 02115. Hydatidiform mole (HM) can precede gestational choriocarcinoma and may represent a transition between normal and malignant trophoblast. The present study was undertaken to determine if oncofetal markers can be used to distinguish malignant from normal trophoblast and, if so, whether HM resembles malignant trophoblast in the expression of these markers. A panel of monoclonal antibodies with known specificities for embryonic or oncofetal antigens was tested in immunofluorescence or immunoperoxidase assays against methanol-fixed frozen sections of 9 normal human placentas from various stages of pregnancy, 10 cases of complete hydatidiform mole, and methanol-fixed human choriocarcinoma cell (CCA) lines BeWo and Jar. Three monoclonal antibodies with reactivity against a variety of human tumors, &SEA-I, MA2, and MA7, reacted with CCA cell lines but not normal placenta or HM. Other monoclonal antibodies to human oncofetal antigens, such as SSEA-3, did not react with trophoblast components of normal placenta, HM or CCA. We are currently expanding this panel of monoclonal antibodies to include other oncofetal markers. To date, our results indicate that certain oncofetal markers can be used to identify malignant trophoblast, and that HM trophoblast does not express these malignancy-associated markers. [Supported by NIH Grant CA 32132.1 40. Specijcity and Activity of Autologous Antibodies Eluted from Membrane Fragments Isolated from Human Ovarian Epithelial Neoplastic Effusions. W. H. KLJTTEH, C. E. WELANDER, H. D. HOMESLEY, AND G. J. DOELLGAST, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103. Membrane fragments, purified from human ovarian epithelial neoplastic effusions, were studied to determine if they had bound immunoglobulin as an indication that patients were capable of forming antibodies to ovarian tumor-associated antigens. Ovarian cyst fluids were obtained from 106 patients; membrane fragments were isolated by ultracentrifugation and column chromatography, washed, and treated with dilute acid to elute any surface associated components. Amounts of membrane-associated IgG, determined by enzyme-linked immunoassay, were found to fluctuate from patient to patient, suggesting variations in immune/responsiveness. Five preparations of autologous membrane-eluted IgG were selected for study and examined by indirect immunofluorescence for reactivity. The antibodies did react with three different human ovarian cell lines and tissue sections from two human ovarian tumors grown in athymic (nude) mice but did not bind to human kidney, uterine, cervical, colon, or malignant melanoma cell lines. The antibodies did not recognize antigens on the following normal or neoplastic tissues: ovary, stomach, cervix, kidney, lung, fallopian tube, colon, small intestine, colon adenocarcinoma, or lung adenocarcinoma. Two of the autologous antibody preparations were capable of mediating complement-dependent cellular cytotoxicity against human ovarian cell lines but not against other normal human cells. These studies indicate that patients with ovarian cancer have the capability to recognize tumor as foreign, to mount a spec$c humoral immune response against tumor-associated cell-surface antigens, and to form antibodies capable of mediating cytotoxicity against ovarian tumor cells. 41. Plasma Ovarian Cancer Antigen NB/70K: Clinical Correlations. A. J. DEMBO,* P-L CnANo,t A. MALKINJ: AND G. I. IJaaAcu,t *Princess Margaret, ?Wellesley, and $Sunnybrook Hospitals, Toronto, Canada M4X 1K9. NB/70K is a glycoprotein antigen derived from ovarian tumor extract by Knauf and Urbach [Canad. Res. 41, 1351 (1981)]. We used a radioimmunoassay to measure plasma NB/70K in following patients since January 1982: women seen in a gynecology clinic (GC) were used to derive the upper limit of normal (mean + 2SD = llKU/ml): healthy female controls (HC); patients with benign gynecologic neoplasms (BN); epithelial ovarian cancer < 3 months postoperative (PoOC); preoperative ovarian cancer (PreOC); liver failure (LF); and renal failure (RF). Results are summarized in the table.
SOCIETY OF GYNECOLOGIC
ONCOLOGISTS-ABSTRACTS
39. Expression of Oncofetal Antigens in Normal Human Placenta, Complete Hydatidiform Mole, and Gestational Choriocarcinoma. D. J. ANDERSON, R. S. BERKOWITZ, D. P. GOLDSTEIN, AND R. KNAPP, New England Trophoblastic Disease Center, Departments of Pathology and Obstetrics and Gynecology, Harvard Medical School. Boston, Massachusetts 02115. Hydatidiform mole (HM) can precede gestational choriocarcinoma and may represent a transition between normal and malignant trophoblast. The present study was undertaken to determine if oncofetal markers can be used to distinguish malignant from normal trophoblast and, if so, whether HM resembles malignant trophoblast in the expression of these markers. A panel of monoclonal antibodies with known specificities for embryonic or oncofetal antigens was tested in immunofluorescence or immunoperoxidase assays against methanol-fixed frozen sections of 9 normal human placentas from various stages of pregnancy, 10 cases of complete hydatidiform mole, and methanol-fixed human choriocarcinoma cell (CCA) lines BeWo and Jar. Three monoclonal antibodies with reactivity against a variety of human tumors, &SEA-I, MA2, and MA7, reacted with CCA cell lines but not normal placenta or HM. Other monoclonal antibodies to human oncofetal antigens, such as SSEA-3, did not react with trophoblast components of normal placenta, HM or CCA. We are currently expanding this panel of monoclonal antibodies to include other oncofetal markers. To date, our results indicate that certain oncofetal markers can be used to identify malignant trophoblast, and that HM trophoblast does not express these malignancy-associated markers. [Supported by NIH Grant CA 32132.1 40. Specijcity and Activity of Autologous Antibodies Eluted from Membrane Fragments Isolated from Human Ovarian Epithelial Neoplastic Effusions. W. H. KLJTTEH, C. E. WELANDER, H. D. HOMESLEY, AND G. J. DOELLGAST, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103. Membrane fragments, purified from human ovarian epithelial neoplastic effusions, were studied to determine if they had bound immunoglobulin as an indication that patients were capable of forming antibodies to ovarian tumor-associated antigens. Ovarian cyst fluids were obtained from 106 patients; membrane fragments were isolated by ultracentrifugation and column chromatography, washed, and treated with dilute acid to elute any surface associated components. Amounts of membrane-associated IgG, determined by enzyme-linked immunoassay, were found to fluctuate from patient to patient, suggesting variations in immune/responsiveness. Five preparations of autologous membrane-eluted IgG were selected for study and examined by indirect immunofluorescence for reactivity. The antibodies did react with three different human ovarian cell lines and tissue sections from two human ovarian tumors grown in athymic (nude) mice but did not bind to human kidney, uterine, cervical, colon, or malignant melanoma cell lines. The antibodies did not recognize antigens on the following normal or neoplastic tissues: ovary, stomach, cervix, kidney, lung, fallopian tube, colon, small intestine, colon adenocarcinoma, or lung adenocarcinoma. Two of the autologous antibody preparations were capable of mediating complement-dependent cellular cytotoxicity against human ovarian cell lines but not against other normal human cells. These studies indicate that patients with ovarian cancer have the capability to recognize tumor as foreign, to mount a spec$c humoral immune response against tumor-associated cell-surface antigens, and to form antibodies capable of mediating cytotoxicity against ovarian tumor cells. 41. Plasma Ovarian Cancer Antigen NB/70K: Clinical Correlations. A. J. DEMBO,* P-L CnANo,t A. MALKINJ: AND G. I. IJaaAcu,t *Princess Margaret, ?Wellesley, and $Sunnybrook Hospitals, Toronto, Canada M4X 1K9. NB/70K is a glycoprotein antigen derived from ovarian tumor extract by Knauf and Urbach [Canad. Res. 41, 1351 (1981)]. We used a radioimmunoassay to measure plasma NB/70K in following patients since January 1982: women seen in a gynecology clinic (GC) were used to derive the upper limit of normal (mean + 2SD = llKU/ml): healthy female controls (HC); patients with benign gynecologic neoplasms (BN); epithelial ovarian cancer < 3 months postoperative (PoOC); preoperative ovarian cancer (PreOC); liver failure (LF); and renal failure (RF). Results are summarized in the table.