A useful antibody panel for differential diagnosis between peritoneal mesothelioma and ovarian serous carcinoma in Japanese cases.

Malignant mesothelioma is increasing in incidence worldwide, including in Japan. However, the accurate pathologic diagnosis of pleural or peritoneal mesothelioma (PM) is sometimes difficult if adequate histologic and immunohistochemical analyses are not undertaken. The aim of this study was to identify a useful antibody panel for distinguishing PM from ovarian serous papillary adenocarcinoma (SC). We obtained 29 PMs (23 epithelioid mesotheliomas and 6 biphasic mesotheliomas) and 20 SCs from our surgical pathology files. Immunohistochemical analysis was undertaken using 13 commercially available antibodies. No significant sex differences in antigen expression among the 29 PMs were observed. The results identified calretinin and thrombomodulin as positive markers and Ber-EP4, MOC-31, CA19-9, and estrogen receptor as negative markers with relatively high sensitivity and specificity for the differential diagnosis of PM and SC. The combination of these positive and negative markers may contribute to accurate diagnosis and adequate therapy for PM and ovarian SC.

Local immune response in serous papillary carcinoma of the endometrium.

OBJECTIVE: Serous papillary carcinomas of the endometrium are aggressive tumors that tend to permeate, in a very extensive fashion, to uterine and adnexal lymphatic and vascular channels at an early stage in their evolution, and are associated with a particularly gloomy prognosis. It is generally thought that even tumors apparently limited to the endometrium or confined to an endometrial polyp have a poor outcome. Our study points towards the value of HLA-DR antigen in the outcome of serous papillary endometrial cancer. Our aim was to assess the HLA-DR expression in inactive, endometrial intraepithelial carcinoma (EIC), and invasive serous carcinoma curretage specimens from the endometrial cavity, suggesting a role in immune response to keep tumor proliferation in check. STUDY DESIGN: Thirty-one cases of inactive endometrium, twelve cases of EIC, and thirty-nine cases of serous papillary invasive carcinoma curettings were evaluated for the detection of HLA-DR monoclonal antigen. T helper (TH) marker (CD4) in the tumor stroma of the relevant cases was also studied, given that it is now known that the dependence of immune responsiveness on the class II antigens reflects the central role of these molecules in presenting antigen to TH cells. RESULTS: HLA-DR was expressed in 20 of 31 inactive endometrium (64.5%), 4 of 12 in EIC (33.3%), and in 10 of 39 serous papillary invasive carcinomas (25.6%). CD4 was expressed in 9 of 31 inactive endometrium (29%), 5 of 12 in EIC (42%), and in 26 of 39 serous papillary invasive carcinomas (67%). CONCLUSIONS: The results showed decreased expression of HLA-DR and increased expression of CD4 as the lesion progressed to malignancy. The aberrant expression of HLA-DR by epithelial cells of inactive endometrium, of EIC and of serous papillary invasive carcinomas agrees with the hypothesis of the inactive endometrium - carcinoma in situ sequence as the usual route for the development of serous papillary invasive carcinoma. The immune attract mechanism by low HLA-DR signaling seems to be of minor importance in the malignant and metastatic potential of the serous papillary endometrial tumours.

[Immuno-therapeutic study of anti-idiotype minibody (single chain Fv-CH3) on ovarian carcinoma bearing mice].

OBJECTIVE: An anti-idiotypic minibody with optimal antigenicity which mimicking ovarian cancer antigen was used for therapeutic research in mice model bearing ovarian cancer. METHODS: Using gene engineering technique, prokaryotic expression vector was constructed by genetic fusion of 6B11scFv to human IgG1 hinge and CH3 region. The fusion protein named minibody was induced with IPTG in E. coli and analyzed with Western blot and inhibition ELISA tests respectively. Twenty human-PBL-SCID mice bearing i.p. Skov3.ip1 cells were divided into two groups (10 per-group), 10 mice were immunized repeatedly by minibody every two weeks for three times. Indirect ELISA test was employed for analyzing the characterization of anti-anti-idiotypic scFv (Ab3). The latent period of ascites growth and the mean survival time were observed respectively. CD4+ and CD8+ T cells from the spleen of immunized mice were assayed by flow cytometry. RESULTS: SDS-PAGE gel electrophoresis showed that a protein band with molecular weight of 50,000 appeared as the expected size after transformation and induction the host bacteria BL21 (DE3). The expressed minibody could be reacted with COC166-9 (Ab1 of 6B11) and binding goat anti-human IgG1 antibody in Western blot. Inhibition ELISA showed minibody had the capacity of binding ovarian cancer monoclonal antibody COC166-9 instead of primal antigen. Ab3 could be detected in the sera of immunized mice with minibody by ELISA test. Ab3 reached the highest at the 14th day after last vaccination and lasted for 6 weeks. The ratio of CD4+/CD8+ was the highest at the 13th day after last vaccination. The latent period of ascites growth were (37.7 +/- 5.5) days and (48.6 +/- 14.3) days (P = 0.04) respectively; while the mean survival time were (42.5 +/- 1.8) days and (59.4 +/- 16.8) days (P = 0.011) in the control and minibody group respectively. CONCLUSIONS: These results demonstrate the successful construction and expression minibody with good immune activities of 6B11scFv and human IgG1 molecules function. Antigenicity is increased without adjuvants and partial humanization is realized. Minibody can induce humoral anti-idiotypic immunity responses against ovarian carcinoma in vivo. When ascites formation was delayed or prevented and the survival was prolonged in minibody group. We expect that minibody may be used as tumor vaccine to ovarian carcinoma in the future clinical trails.

Gains and losses of CD8, CD20 and CD56 expression in tumor stroma-infiltrating lymphocytes compared with tumor-associated lymphocytes from ascitic fluid and lymphocytes from tumor draining lymph nodes in serous papillary ovarian carcinoma patients.

Serous papillary ovarian cancer (SPC) is a highly aggressive tumor. About two-thirds of women have advanced disease at the time of diagnosis. Although many women with disseminated disease respond at first to combinations of surgery and chemotherapy, nearly 90% of tumors recur and women die of disease. Update progress in our knowledge of tumor-associated antigens and insight into mechanisms involved in immune-mediated recognition of these antigens, have provided a strong starting point for using the immune system as a model for novel therapy. In this study we determined the immunological profile of tumor-infiltrating lymphocytes (TILs), tumor-associated lymphocytes (TALs) in ascitic fluids, and lymphocytes from tumor draining regional lymph nodes (LNs) in SPC patients by CD20 (L26), CD8, and CD56 immunostaining. We examined 14 cases of TILs, 15 cases of TALs and 19 cases of LNs. TILs were infiltrating tumor stroma. No significant difference was detected in TILs, TALs and LNs in the expression of the B-cell marker CD20. In contrast, CD8 (T-cytotoxic) and CD56 (natural killer cell, NK) markers were dominant in LNs and TALs, but not in TILs. We conclude that SPC tumor lymphocytic infiltrate demonstrates a deplete T cytotoxic (CD8+) and NK cell (CD56+) immunophenotypic profile. This might in part explain the poor clinical outcome of the disease.

Prolonged symptom-free survival in a patient with persistent primary peritoneal carcinoma and a rising CA-125: a note of caution.

BACKGROUND: The optimal management of patients with ovarian and primary peritoneal carcinomas who experience an elevation of the serum CA-125 antigen level following the completion of therapy, and who remain without other clinical evidence of recurrent/progressive disease, remains controversial. CASE: A patient with primary peritoneal carcinoma cared for in the Gynecologic Cancer Program of the Cleveland Clinic Foundation has experienced prolonged symptom-free survival (>4 years) after a documented tripling of her persistently elevated postchemotherapy serum CA-125 without the reinstitution of cytotoxic therapy. CONCLUSION: This case emphasizes that caution must be exercised when electing to initiate second-line treatment solely on the basis of an abnormal tumor antigen level.

Induction of ovarian tumor-specific CD8+ cytotoxic T lymphocytes by acid-eluted peptide-pulsed autologous dendritic cells.

OBJECTIVE: To evaluate the potential of dendritic cells pulsed with acid-eluted peptides derived from autologous ovarian cancer cells for eliciting a tumor-specific cytotoxic T cell response in women with advanced ovarian cancer. METHODS: CD8+ T lymphocytes derived from peripheral blood mononuclear cells stimulated in vitro with autologous ovarian tumor peptide-pulsed dendritic cells were tested for their ability to induce an HLA class I-restricted cytotoxic T lymphocyte response against autologous tumor cells. To correlate cytotoxic activity by cytotoxic T lymphocytes with T cell phenotype, we used two-color flow cytometric analysis of surface markers and intracellular cytokine expression (interferon-gamma versus interleukin-4). RESULTS: CD8+ cytotoxic T lymphocyte responses against autologous ovarian tumor cells were elicited in three consecutive women who had advanced ovarian cancer. Although cytotoxic T lymphocyte populations from all women expressed strong cytolytic activity against autologous tumor cells, they did not lyse autologous lymphoblasts or Epstein-Barr virus-transformed cell lines, and they showed negligible cytotoxicity against the natural killer-sensitive cell line K-562. Cytotoxicity against the autologous tumor cells was significantly inhibited by anti-HLA class I (W6/32) and anti-HLA-A2 (BB7-2) monoclonal antibodies. CD8+ cytotoxic T lymphocytes expressed variable levels of CD56 and preferentially expressed interferon-gamma rather than interleukin-4. CONCLUSIONS: Peptide-pulsed dendritic cells induced specific CD8+ cytotoxic T lymphocytes that killed autologous tumor cells from women with advanced ovarian cancer. This finding might contribute to the development of active or adoptive immunotherapy for residual or resistant ovarian cancer after standard surgery and cytotoxic treatment.

Immunization of ovarian cancer patients with a synthetic Lewis(y)-protein conjugate vaccine: a phase 1 trial.

As the initial step in developing carbohydrate-based vaccines for the treatment of ovarian cancer patients in an adjuvant setting, 25 patients were immunized with a Lewis(y) pentasaccharide (Le(y))-keyhole limpet hemocyanin (KLH)-conjugate vaccine together with the immunological adjuvant QS-21. Four different doses of the vaccine, containing 3, 10, 30, and 60 microg of carbohydrate were administered s.c. at 0, 1, 2, 3, 7, and 19 weeks to groups of 6 patients. Sera taken from the patients at regular intervals were assayed by ELISA for reactivity with naturally occurring forms of Le(y) (Le(y)-ceramide and Le(y) mucin) and by flow cytometry and a complement-dependent cytoxicity assay for reactivity with Le(y)-expressing tumor cells. The majority of the patients (16/24) produced anti-Le(y) antibodies as assessed by ELISA, and a proportion of these had strong anti-tumor cell reactivity as assessed by flow cytometry and complement-dependent cytotoxicity. One serum, analyzed in detail, was shown to react with glycolipids but not with glycoproteins or mucins expressed by ovarian cancer cell line OVCAR-3. The vaccine was well tolerated and no gastrointestinal, hematologic, renal, or hepatic toxicity related to the vaccine was observed. On the basis of this study, Le(y)-KLH should be a suitable component for a polyvalent vaccine under consideration for the therapy of epithelial cancers.

Correlations of serum CA125 level and computerized tomography (CT) imaging with laparotomic findings following intraperitoneal chemotherapy in patients with ovarian cancer.

UNLABELLED: The aim of this study was to evaluate the role of serum CA125 levels and computerized tomography (CT) scans in predicting pathologic response of intraperitoneal chemotherapy in patients with ovarian cancer. We prospectively analyzed serum CA125 levels and abdominopelvic CT scans obtained after the completion of intraperitoneal chemotherapy in 52 patients with ovarian cancer and compared the results with subsequent laparotomic findings, which served as the gold standard for statistical analysis. Laparatomy revealed either microscopic or macroscopic residual disease in 20 patients, while 32 patients were completely tumor-free. CA125 levels correlated significantly with laparotomic findings (p=0.003, u=1405). Median CA125 values in patients with residual tumors and in tumor-free patients following intraperitoneal chemotherapy were 14.6 (1-775) and 7.2 (1-37) U/ml, respectively. Although CT-imaging and CA 125 levels had a high specificity (100% and 96.9%, respectively), they showed a low sensitivity rate (50% and 40%, respectively). Similarly, despite high positive predictive values (100% and 88.9%, respectively), the negative predictive values were 76.2% and 72.1%, respectively. CONCLUSION: Although highly specific, CT scans and CA125 levels do not accurately indicate the presence of disease. Due to a high false-negative rate, a normal CT scan or a normal CA125 value is not sufficient to replace a laparotomy.

Immunohistochemically detecting target antigens in patient biopsies for tailoring monoclonal antibody based cancer therapy.

Immunohistochemical analysis of biopsies, cytology specimens or surgical resection specimens using antibodies directed towards tumor-associated antigens, lineage or differentiation antigens is a technique often used by surgical pathologists to aid in establishing the correct histologic classification of malignant tumors. With the proliferation of experimental approaches to cancer treatment using monoclonal antibodies as targeting agents, it is anticipated that surgical pathologists will increasingly be receiving requests from clinicians to define the antigen profile in biopsy specimens, even when not necessary to render the correct tumor classification. Clinicians may use the immunohistochemically delineated antigen profiles provided by surgical pathologists to plan tailored treatment regimens utilizing monoclonal antibodies to the antigens expressed in the tumor biopsy to target anticancer therapeutic agents. Some of the potential problems in such a process might include the differing sensitivities, and perhaps specificities, of the antibodies used for analyzing the surgical pathology biopsy specimens compared to the monoclonal antibodies actually used in vivo. Our approach to this dilemma is to develop murine monoclonal antibodies to tumor-associated antigens that can reliably be used to detect antigens in routinely processed surgical pathology specimens as a starting point for further therapeutic monoclonal antibody development.

[In vitro study of 6B11GM to induce cellular immunity in patients with ovarian carcinoma].

OBJECTIVE: In order to explore the possibility of ovarian carcinoma anti-idiotypic single chain antibody (6B11scFV) and human granueocyte-macrophage colony stimulating factor (hGM-CSF) fusion protein 6B11GM as tumor vaccine. METHODS: Mononuclear cells, T cells and monocyte used as antigen presenting cell (APC) were separated from peripheral blood, and tumor cells were obtained from ascitic fluid in the same patients. In vitro T cell proliferation and autologous tumor cell cytotoxicity assay were applied. RESULTS: 6B11GM could induce T cell proliferation in vitro which was antigen specific. Cytotoxicity of mononuclear cells to autologous tumor cells increased after primed with 6B11GM. CONCLUSION: 6B11GM could induce efficient cellular immunity in patients with ovarian carcinoma, hopefully may be used for ovarian carcinoma vaccine.

Immunophenotypic analysis of ovarian and testicular Müllerian papillary serous tumors.

Intratesticular Müllerian papillary serous tumors lacking stromal invasion are uncommon neoplasms whose immunophenotypic properties have not been studied extensively. We present such information here and compare it with information from a group of ovarian papillary serous tumors of low malignant potential ("borderline serous tumors") that are morphologically identical. We compared the histologic features of our index case of intratesticular Müllerian papillary serous tumor with those of nine ovarian papillary serous tumors. We then evaluated both the index case and the ovarian tumors with antibodies against carcinoembryonic antigen, LeuM1, CA125, estrogen receptors, progesterone receptors, cytokeratin 7, and cytokeratin 20, by use of established immunohistochemical techniques. The testicular and ovarian tumors were morphologically indistinguishable. The intratesticular Müllerian papillary serous tumor expressed LeuM1, CA125, estrogen receptors, progesterone receptors, cytokeratin 7, and weak cytokeratin 20; carcinoembryonic antigen was not expressed. All of the ovarian papillary serous tumors expressed CA125, estrogen receptors, and cytokeratin 7. Eight of nine expressed progesterone receptors. Five of nine stained with LeuM1. Two of nine were focally weakly positive with cytokeratin 20. LeuM1 expression helps distinguish testicular papillary serous tumors from mesothelial proliferations, which might seem morphologically similar. The immunophenotype of intratesticular and female genital papillary serous tumors is similar; this similarity extends to expression of estrogen and progesterone receptors, which is rare in neoplasms in men, especially among testicular neoplasms.

Vaccination with monoclonal anti-idiotypic antibody on immunocompetent mice bearing human ovarian carcinoma.

OBJECTIVE: To observe the effects of anti-idiotypic monoclonal antibody 6B11 against ovarian carcinoma SKOV3 on immunocompetent mice BCF1 both in vivo and in vitro, so as to investigate the possibility of using it as a tumor vaccine. METHODS: After immunization with 6B11 and normal mice (NM) IgG respectively on 2 groups of BCF1, blood, lymphocytes and tumor tissues were taken every other day. Ab3 was tested from blood samples. Subpopulations of lymphocytes were examined by FCM. The lymphocytes from immunized BCF1 were also cultured with SKOV3 to observe the chemotaxis and killing effects. Serial tissue sections were taken from BCF1 after immunization by SRCA implantation of SKOV3. TIL and visible cancer cells were examined carefully and compared with those in the controls. RESULTS: Ab3 rose quickly after immunization with 6B11 but lowered down gradually till the 9th week. The CD4+/ CD8+ ratio of BCF1 changed markedly after immunization with 6B11. The immunized lymphocytes showed a beautiful chemotaxis with and killing effect on SKOV3. During in vivo examinations, TIL were found significantly earlier in the immunized BCF1 than in the controls and reached the peak earlier in the former (on the 6th day) than in the latter, while the viability of tumor cells was vice versa between the two groups. CONCLUSION: 6B11 may be used as a vaccine for not only active immunization but also prevention of ovarian carcinoma.

Development and characterization of an IL-4-secreting human ovarian carcinoma cell line.

Human ovarian carcinoma cell lines were genetically engineered to secrete the cytokine interleukin-4 (IL-4) by retroviral-mediated gene transduction. These cells were transduced with the LXSN retroviral vector containing the human IL-4 gene and the neomycin resistance selection marker. Numerous IL-4-secreting clones were isolated from different papillary serous carcinoma cell lines, including SKOV-3, UCI-101, and UCI-107, and one clone derived from UCI-107 extensively characterized. This clone, termed UCI 107E IL-4 GS, was shown to constitutively express high levels of IL-4 (i.e., 900 to 1300 pg/ml/10(5) cells/48 hr) for over 35 passages and 6 months of study. Like the parental cell line (UCI-107), UCI 107E IL-4 GS cells expressed MHC class I and Her-2/neu surface antigens but did not express detectable MHC class II, ICAM 1, CA 125, or IL-4 receptors. No increase in expression of surface proteins was noted between parental and UCI 107E IL-4 GS. The morphology of this clone did not differ from that of the parental or LXSN vector control cells; however, parental cells had a faster growth rates than transductants. UCI 107E IL-4 GS was sensitive to gamma irradiation since as little as 2500 rad killed most of the cells within 10 days of irradiation. However, after irradiation, IL-4 secretion continued until about Day 8. The potential use of these IL-4-secreting ovarian carcinoma cells as vaccines for woman with advanced ovarian cancer will be discussed.

CD44 variant expression is a common feature of epithelial ovarian cancer: lack of association with standard prognostic factors.

PURPOSE: CD44 is a hyaluronic acid receptor that exists as a standard 90-kd form (CD44S) as well as several CD44 variant isoforms produced through alternative splicing. Expression of CD44 variants is associated with clinically aggressive behavior in some human tumors. The purpose of the present study is to define the expression of CD44 variant isoforms in ovarian cancer and to investigate whether the expression of these molecules is associated with adverse prognosis. MATERIALS AND METHODS: Six specimens of normal ovarian surface epithelium (NOSE) and 31 separate cases of newly diagnosed ovarian cancer were studied by a combination of reverse-transcription polymerase chain reaction (RT-PCR) and immunoperoxidase staining. Clinical correlation was made between CD44 variant expression and stage (I/II v III/IV), residual disease (< or = 2.0- v > 2.0-cm mass), age (< or = 65 v > 65 years), histology (papillary serous v other), grade, and survival. RESULTS: RT-PCR analysis revealed that NOSE predominantly expressed transcripts for CD44S, as well as a restricted pattern of transcripts characteristic of CD44 splice variants. CD44S and CD44 variant exon nine sequences (CD44-9v) were focally expressed in one of two NOSE specimens examined by immunoperoxidase staining. In comparison, the majority (71%) of ovarian cancer specimens expressed a complex pattern of CD44 splice variants by RT-PCR analysis. Immunoperoxidase studies revealed that the majority of ovarian cancer specimens expressed both CD44S and CD44-9v, whereas expression of sequences from variant exons 3, 4, and 6 was uncommon. There was no association between CD44 variant expression (transcript or protein) and stage, residual disease, age, histology, grade, or survival. CONCLUSION: Expression of CD44S and CD44-9v is a common feature of epithelial ovarian cancer cells. The lack of a significant association between CD44 variant expression and prognosis suggests that other factors may be more important in determining the clinical behavior of this disease.

[A case of subacute sensory neuropathy associated with extraovarian serous papillary adenocarcinoma of the peritoneum].

We reported a case of subacute sensory neuropathy. A 78-year-old woman was admitted to Kenwakai Hospital because of progressive numbness in her hands and feet. Four months before admission, numbness and tingling sensations appeared in her hands and feet, and subsequently she felt difficulty in skilled finger movement. On general examination, she was found to have a mass in the right lower abdomen. Neurological examination revealed marked loss of position sense and vibratory sense in the distal extremities, and mild reduction of sensation to pinprick and light touch in the distal extremities. Stretch reflexs were depressed in the upper limbs and absent in the lower limbs. Her gait was unsteady and Romberg's sign was positive. She showed no cranial nerve dysfunction, cerebellar ataxia, muscle weakness, and autonomic dysfunction. Blood examination revealed high TTT (11.3Kunkel U), high ZTT (16.4Kunkel U) titer. Tumor markers were normal except for CA125 (93 U/ml). The cerebrospinal fluid showed 48 mg/dl of protein, 10.6 mg/dl of IgG. and an almost normal cell count (5.3/mm3). Serum was tested by immunohistochemical staining. Only the cytoplasm of neurons in the dentate nucleus and brain stem was stained on a rat's brain. Sural nerve biopsy showed a severe loss of large myelinated fibers. An exploratory laparotomy revealed a peritoneal tumor, 5 cm in diameter, and it was removed. During the surgery, other than a few rice-sized nodules in the cul-de-sac, there was no evidence of tumor in bilateral ovaries. The tumor was proven to be a serous papillary adenocarcinoma with psammoma bodies resembling ovarian cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous release of interleukin-6 by primary cultures of lymphoid and tumor cell populations purified from human ovarian carcinoma.

Interleukin-6 (IL-6) is a cytokine that has been implicated as a growth factor in human ovarian carcinoma, yet the in vivo source of IL-6 in patients remains undefined. We measured IL-6 by ELISA in cell-free ascites (CFA) of 19 patients with ovarian carcinoma. IL-6 was detectable in all samples (mean level 3.3 ng/ml). To identify the cellular source of IL-6, we measured this cytokine by ELISA in 24-48 h supernatants of cultured lymphocyte-, macrophage-, and tumor cell-enriched populations purified from three solid ovarian carcinomas by centrifugal elutriation. All cell populations spontaneously released IL-6; however, tumor cells and tumor-associated macrophage released levels of IL-6 that greatly exceeded those released by tumor-associated lymphocytes. Kinetic studies revealed that IL-6 was detectable at 6 h and that levels increased in all cultures examined over a 48 h time course. These data suggest that both tumor and infiltrating host cells may be the source of the high levels of IL-6 found in carcinomatous ascites. Furthermore, although all three cell types examined may contribute to IL-6 production in patients with ovarian carcinoma, tumor cells are perhaps the most clinically significant source.

[Soluble interleukin-2 receptor level in the sera and ascitic fluids in patients with ovarian cancer].

In 31 patients with ovarian cancer, the sIL-2R level of the sera and ascitic fluids were measured by ELISA, to investigate the inhibitive effect of sIL-2R purified from ascitic fluids on normal lymphocyte transformation, stimulated with phytohemagglutinin (PHA). The results showed that the sera sIL-2R levels in the patients were much higher than those in the normal controls (857 +/- 428kU/L vs 235 +/- 90kU/L, P < 0.001). The sera sIL-2R levels in mucinous cancer were significantly higher than those in serous cancer (988 +/- 539kU/L vs 488 +/- 233kU/L P < 0.01). But no obvious correlation was observed with the histopathological grading, nor with metastasis. Higher levels of sIL-2R were also observed in the ascitic. The normal lymphocyte transformation stimulated with PHA was significantly inhibited by high sIL-2R purified from the ascitic fluids.

[Production and identification of a monoclonal antibody against a tumor associated antigen from ovarian epithelial carcinoma].

The splenocyte of BALB/c mice, immunized with soluble and ovarian serous papillary cystedenoma-associated antigen CA925, was fused with NS-1 myeloma cell strain to produce a monoclonal antibody. 5 cell strains of the monoclonal antibody with continuous secretion were obtained. The fusion openings were used as code names: OC4D9, OC7E10, OC1B4, OC3B8, and OC9B9, their titers were 1: 10(7), 1: 10(7), 1: 10(6), 1: 10(4) and 1: 10(5) respectively. Ig subgroups were IgM and IgG. The chromosomes showed the characteristics of their parents. The 5 strains of the monoclonal antibody obtained presented specific reactions to CA925, no positive reaction with normal ovarian tissues or leiomyoma of the uterus were seen, and there were weak reactions with carcinomas of the lung, the stomach, the kidney, the esophagus and the rectum. Immunohistochemical tests proved that the monoclonal antibody produced was specific against ovarian epithelial carcinoma, and it might offer a means to the diagnosis and treatment of malignant ovarian tumors.

Are CASA and CA125 concentrations in peripheral blood sourced from peritoneal fluid in women with pelvic masses?

BACKGROUND: The Cancer associated serum antigen (CASA) and CA125 assays used in the management of ovarian cancer measure distinct high molecular weight glycoproteins. The mechanisms of secretion of these molecules into the peripheral circulation are not clearly understood. METHODS: Concentrations of CASA and CA125 were assessed in peripheral blood, blood from veins draining ovarian and omental tumors, and peritoneal fluid in 20 women with pelvic masses. RESULTS: There was a near perfect correlation between peripheral vein and ovarian vein concentrations for both markers; concentrations in omental veins were higher than in peripheral veins in only a small proportion of cases, whereas the concentration in peritoneal fluid was universally much higher than in blood. CONCLUSIONS: These studies suggest a similar route of entry into the peripheral circulation and a similar half-life for these glycoproteins. These data provide no support for the hypothesis that a significant contribution to CA125 concentrations comes from peritoneal release by mesothelial cells rather than tumor cells, because the relative CA125 concentrations between compartments were similar to those of CASA within patients. The lack of a gradient between CASA levels in peripheral blood and tumor draining veins suggests that the CASA half-life is much longer than that predicted in animal studies. CA125 and CASA in peripheral blood are probably derived from markers secreted into peritoneal fluid and lymph, rather than directly into the bloodstream.