Sensitivity enhancement of the cytologic detection of cancer cells in effusions by monoclonal antibodies.

Cells from 229 pleural and peritoneal spontaneous fluids and 51 peritoneal lavage fluids from patients with neoplastic and nonneoplastic diseases were studied by indirect immunofluorescence with two monoclonal antibodies; MBr1, prepared against breast carcinoma, and MOv2, prepared against ovarian carcinoma. The results were correlated with those obtained by conventional cytologic methods. A cytologic diagnosis of metastatic carcinoma was established in about 50% of the fluids examined. Sixty percent of the cytologically malignant fluids contained tumor cells reactive with at least one of the two monoclonal antibodies tested. The specificity of the labeling was confirmed by immunoelectron microscopy. In addition, 16 fluids with a negative cytologic diagnosis contained cells strongly immunopositive with MBr1 and/or MOv2. Reactive mesothelial cells were consistently negative. These results suggest that antibodies MBr1 and MOv2 are able to identify cancer cells that do not fully meet conventional morphologic criteria for malignancy. The two reagents, when used in support of cytologic analysis, may substantially reduce the number of false negative cytologic diagnoses of fluids from patients with breast and ovarian carcinomas.

A double determinant radioimmunoassay Mov2-MOv8 for monitoring ovarian carcinomas: definition of the methodology.

A double-determinant radioimmunoassay for the detection of circulating antigens associated with human ovarian carcinoma was developed using two monoclonal antibodies: MOv2 and MOv8 employed respectively as catcher and tracer. The development of the method through three different procedures enabled us to detect the presence of CaMOv2-CaMOv8 carrying molecules in 14 out of 15 ascitic fluids from ovarian carcinoma patients whose tumors were found to be positive with MOv2 and MOv8 monoclonal antibodies by immunofluorescence. Moreover, 13 out of 15 ovarian carcinoma patients presented high levels of antigen in their serum (60-170 Ua/ml). Low levels of antigen were observed in the normal population, the values ranging from 30-40 Ua/ml. However, in 13 out of 100 apparently healthy women high levels of antigen were found in the serum.

Fc receptor-like structures on in vitro-cultured human ovarian tumor cells.

Four ovarian cystadenocarcinomas cultured in vitro were tested by a radioisotopic method with sera from cancer patients or healthy donors to search for a possible specific antitumor immune response of patients bearing ovarian tumors. However, the ovarian tumor cells were found to bear on their membrane surface structures able to bind immunoglobulins from any tested serum, thus making impossible the detection of a hypothetical specific antitumor antibody. These structures were demonstrated to bind the Fc portion of the Ig and were therefore similar to the Fc receptors described on various normal cells, particularly of the immunocompetent compartment.

Adjuvant treatment with melphalan in ovarian carcinoma with no residual disease following surgery.

Forty-nine patients classified after surgery and complete non-surgical restaging as "no residual disease" were treated with adjuvant chemotherapy. Thirty-nine patients had ovarian carcinoma and 10 borderline tumors. All patients had geographic inaccessibility. Domiciliary treatment with melphalan at the dose of 10 mg/day p.o. for 5 consecutive days every 4 weeks for 12 cycles was used. Within 6 months from the end of adjuvant treatment a second restaging with peritoneoscopy and peritoneal cytology was performed. The median administered dose of melphalan was 575 mg. No patient with a borderline tumor relapsed. Nine patients with ovarian carcinoma relapsed (23%): 4/10 at stage II-III and 5/29 (17%) at stage I. The relapse-free survival at 96 months was 77% for stage I patients and 73% for all patients. The overall survival was 87% for stage I patients and 81% for all patients. Mild myelo-depression was evident in 65% of patients. No case of acute nonlymphocytic leukemia was observed.

Immunohistochemical reactivity of a monoclonal antibody prepared against human ovarian carcinoma on normal and pathological female genital tissues.

The reactivity profile of the monoclonal antibody (MAb) MOv18, raised against a poorly differentiated ovarian carcinoma specimen, was studied on normal tissues and tumors from the female reproductive system and on the kidney, which like the oviducts, vagina and uterus, also derives from the intermediate mesoderm. The obtained results indicate that MOv18 recognizes an epitope present on the normal epithelium of the oviducts, on 14-week old fetal kidney and, focally, on proximal and distal tubules of normal adult kidney. A strong reactivity was found on ovarian carcinomas, on invasive squamous carcinomas of the cervix and on endometrial carcinomas and hyperplasias. The antigen recognized by MOv18 (CaMOv18) therefore seems to be an epithelial cell marker associated with intermediate mesoderm differentiation, which can be derepressed during the neoplastic transformation of the ovary and the uterus.

Problems after hysterectomy. A comparative content analysis of 60 interviews with cancer and non-cancer hysterectomized women.

Sixty patients who had undergone hysterectomy for neoplastic pathologies (30 cases) and benign pathologies (30 cases) were interviewed with the aim of understanding the relationship they had with the disease, the loss of the uterus and sexuality. Out of the cancer group 21 cases showed fear of recurrence of the disease, 19 cases showed sexual dysfunctions, while only 9 patients referred to having experienced the loss of the uterus as a traumatic event for their femininity. Non-cancer patients revealed reactive sexual difficulties. Out of this sample, 17 cases described their sexual life as unsatisfying.

Characterization of human ovarian carcinoma-associated antigens defined by novel monoclonal antibodies with tumor-restricted specificity.

Three new monoclonal antibodies (MAbs) (MOv16, MOv18 and MOv19) were raised against human ovarian carcinoma. To obtain more specific reagents than those produced so far, we adopted the following experimental approach which consisted of: the selection of a poorly differentiated ovarian carcinoma which was unreactive with all the MAb previously selected in our laboratory; and the application of a particular immunization protocol. The reactivity of the selected MAbs was studied by solid-phase RIA on live and fixed cells from tumor cell lines and by immunofluorescence on frozen sections from surgical specimens. The MAb MOv16 reacted with 60% of ovarian carcinomas as well as with a high percentage of other carcinomas and with some normal tissues. In contrast, MOv18 and MOv19 appeared to have restricted specificities for ovarian carcinomas and cystadenomas. Reactivity on other carcinomas was only observed in a few cases and no reactivity was found on non-epithelial tumors or normal tissues. Immunoprecipitation experiments indicated that MOv16 recognizes a 48-50-kDA protein, whereas MOv18 and MOv19 both identify a 38-40 kDA glycoprotein band. Cross-competition experiments, together with a double-determinant immunoradiometric assay which uses MOv18 as catcher and MOv19 as tracer, suggested that they recognize different epitopes carried by the same molecule. The affinity constants of MOv18 and MOv19 were estimated to be in the range of 10(8)-10(9) M-1. Taken together, the properties of these antibodies, their restricted ovarian tumor specificities and relative high affinity constants, suggest that they could represent promising tools for in vivo applications.