VISTA expression is associated with a favorable prognosis in patients with high-grade serous ovarian cancer.

Blockading programmed death ligand 1 (PD-L1) shows promising results in patients with some cancers, but not in those with ovarian cancer. V-domain Ig suppressor of T cell activation (VISTA) is a recently discovered immune checkpoint protein that suppresses T cell activation. This study aimed to investigate the expression and clinical significance of VISTA in ovarian cancer as well as its relationship with PD-L1. VISTA and PD-L1 levels in 146 ovarian cancer samples were assessed using immunohistochemistry. We investigated the association between VISTA and other clinicopathological variables, including survival. The associations between the VISTA-encoding C10orf54 gene, other immune checkpoints, and survival were analyzed. VISTA was detected in 51.4% of all samples and 46.6% of PD-L1-negative samples; it was expressed in 28.8%, 35.6%, and 4.1% of tumor cells (TCs), immune cells (ICs), and endothelial cells, respectively. Furthermore, VISTA expression was associated with pathologic type and PD-L1 expression. Moreover, VISTA expression in TCs, but not in ICs, was associated with prolonged progression-free and overall survival in patients with high-grade serous ovarian cancer. The expression of C10orf54 mRNA was associated with prolonged overall survival and immune escape-modulating genes. These results showed that VISTA expression in ovarian tumor cells was associated with a favorable prognosis in patients with high-grade serous ovarian cancer; however, additional studies are required to better understand the expression and role of VISTA in ovarian cancer.

IL-27 suppresses SKOV3 cells proliferation by enhancing STAT3 and inhibiting the Akt signal pathway.

Ovarian cancer continues to be the most lethal gynecologic malignancy worldwide. IL-27 is a novel member of the IL-12 cytokine family. The aim of this study was to investigate the effects of IL-27 on the ovarian cystadenocarcinoma cell line SKOV3 and determine possible mechanisms underlying its effect. We stably transfected an IL-27 plasmid, empty vector, IL-27 shRNA or negative control into SKOV3 cells. Cell proliferative activity was evaluated using a WST-1 cell proliferation assay kit. Cell viability was quantified by measurements of lactate dehydrogenase release. The mRNA levels of nine genes were tested by q-PCR. Western blotting was used to verify apoptosis and signal pathways. We found that the IL-27 plasmid significantly enhanced cytotoxicity and inhibited the proliferation of SKOV3 cells. Caspase-3 protein was augmented by IL-27 plasmid and abated by IL-27 shRNA. The incremental expression of IL-27 activated the STAT3 pathway and attenuated the Akt pathway. The over-expression of IL-27 could significantly upregulate a series of antitumor cytokines including IL-6, IL-12 and interferon-γ and down-regulate protumor factors such as TLR4 and NF-κB1. Our data show that IL-27 has direct antitumor capacity in ovarian cancer cells via enhancing apoptosis by inducing the STAT3 pathway and restraining the Akt pathway. Précis: IL-27 enhanced the cytotoxicity and suppressed the proliferation of ovarian cancer cells by activating STAT3 and inhibiting the Akt signal pathway. IL-27 plays an important role in antitumor activity against epithelial ovarian cancer.

Serum phenylalanine concentrations in patients with ovarian carcinoma correlate with concentrations of immune activation markers and of isoprostane-8.

Increased blood concentrations of essential amino acid phenylalanine are common in patients with HIV infection, in trauma and sepsis and in patients with cancer. The reason for this phenomenon is still unclear. However, all these clinical conditions are known to be linked with inflammation and immune activation. Oxidative stress resulting from chronic immune activation and inflammation could impair activity of phenylalanine (4)-hydroxylase (PAH) and thus give rise to increased phenylalanine concentrations. We therefore examined in 20 patients with ovarian cancer a possible association of serum concentrations of phenylalanine and tyrosine with immune activation markers 75 kDa soluble tumor necrosis factor-alpha receptor (sTNF-R75) and neopterin, and of oxidative stress marker isoprostane-8. Phenylalanine concentrations were higher in patients with higher FIGO stage and correlated with concentrations of sTNF-R75 (rs=0.441) and neopterin (rs=0.346; both p<0.05). No such correlations existed for tyrosine levels. The phenylalanine to tyrosine ratio (phe/tyr), an estimate of PAH activity, correlated somewhat stronger with sTNF-R75 (rs=0.549; p<0.01) and neopterin (rs=0.497; p=0.01). Finally, phenylalanine concentrations correlated with isoprostane-8 concentrations (rs=0.450, p=0.02). Correlations of phenylalanine and phe/tyr with immune activation markers point to a potential role of inflammation and immune activation in the accumulation of phenylalanine. The relationship between oxidative stress marker isoprostane-8 and phenylalanine as well as sTNF-R75 concentrations suggests a link between reactive oxygen species formed during chronic immune activation and inflammation and the decline of PAH activity, which might underlie the increase of phe/tyr (248 words).

Benign inflammatory pancreatic mucinous cystadenomas mimicking locally advanced cystadenocarcinomas. Presentation of 3 cases.

We report 3 cases of benign mucinous cystadenoma of the pancreas mimicking, both clinically and on imaging findings, locally advanced cystadenocarcinoma spreading to neighbouring organs (stomach, splenic and mesenteric vessels, and diaphragm). Surgical resection was performed in light of the suspicion of invasive carcinoma in all 3 cases. Histological examination of the resected specimens showed entirely benign mucinous cystadenomas associated with marked peri-tumoural inflammation that accounted for the pre-operative misdiagnoses. All 3 patients are alive 40, 47 and 54 months after surgery without evidence of tumour relapse. These cases indicate that surgery must be considered in patients with cystic tumour of the pancreas suggesting locally advanced cystadenocarcinoma, even when pre-operative imaging findings suggest tumour extension into neighbouring organs.

Levels of serum neopterin are increased in pancreatic cancer patients and correlate with the prognosis.

UNLABELLED: Neopterin has been recognized as a valid marker for cellular immune activation. Raised neopterin levels indicate the stimulation of macrophages and indirectly T-cell activation. So far no data is available on serum neopterin in pancreatic cancer patients. PATIENTS: In this prospective clinical study serum neopterin values were evaluated in 83 patients with adenocarcinoma of the pancreas (PC), 47 patients with chronic pancreatitis (CP), 8 patients with cystadenocarcinoma (CA) of the pancreas and 24 healthy controls (HC). RESULTS: Serum neopterin was significantly elevated in PC (p < 0. 05) and CA (p < 0.04) as compared to HC. There was no difference found between CP and HC. Pancreatic cancer patients with neopterin levels above 2 pmol/ml had a significantly better survival (p < 0. 05) regardless of stage. In stage III and IV (UICC) this difference was highly significant (p < 0.001). Serum levels of neopterin in resectable patients were also significantly correlated with increased survival and in multivariate analysis proved to be an independent prognostic factor. Neopterin in PC was neither correlated with sex, resectability nor with CA 19/9 and CEA. CONCLUSIONS: Patients suffering from PC who did show activated cellular immune response reflected in elevated neopterin levels above 2 pmol/ml had a significantly better prognosis regardless of tumor stage. In advanced stages elevated neopterin concentrations were significantly associated with increased survival. Cellular immune response seems to influence survival in these advanced stages to a higher degree as expected. These findings underline the possibility for supportive immunotherapy in this patient group.

Giant syncytia and virus-like particles in ovarian carcinoma cells isolated from ascites fluid.

Ovarian cancer cells were isolated from ascites fluid of 30 different patients diagnosed with cystadenocarcinoma of ovaries. Large colonies of malignant ASC cells were observed during the first week of cell growth in vitro. Colony formation was followed by fusion of cells and formation of large multinucleated and highly vacuolated syncytia. In contrast, cells isolated from the ascites fluid produced by patients with benign mucinous cystadenoma of ovaries did not form syncytia. Nonmalignant Brenner tumor cells, isolated from the ascites fluid, also did not form syncytia. Syncytia, but not the nonmalignant tumor cells, were immunofluorescence stained with an anti-human immunodeficiency virus type 1 (HIV-1) gp120 monoclonal antibody (MAb) and MAb RAK-BrI. Both MAbs recognized cancer-associated antigens RAK (for Rakowicz markers) p120, p42, and p25. Exposure of ASC cells to either the anti-HIV-1 gp120 MAb or MAb RAK-BrI inhibited syncytium formation. PCR with HIV-1 Env-derived primers revealed DNA sequences with over 90% homology to HIV-1 gp41 in syncytia and in ovarian cancer cells but not in normal ovary cells. Electron microscopic analysis revealed viral particles, hexagonal in shape (90 nm in diameter), with a dense central core surrounded by an inner translucent capsid and dense outer shell with projections. Negative staining detected membrane-covered particles (100 to 110 nm in diameter) in the cell culture medium. Incubation of normal breast cells with viral particles resulted in drastic morphological changes and syncytium formation by the transformed breast cells. The cytopathic effects of the identified virus resembled those of spumaviruses, which, in addition to their epitopic and genetic homology to HIV-1, might suggest a common phylogeny.

[The construction and expression of 6B11scFv anti-idiotypic antibody and human granulocyte-macrophage-colony stimulating factor in Escherichia coli].

OBJECTIVE: To enhance the antigenicity of an anti-idiotypic single chain antibody 6B11 mimicking ovarian cancer antigen. METHODS: Using DNA recombinant technique, a recombinant fusion protein expression vector was constructed. This vector linked 6B11scFv cDNA and human GM-CSF with a linker. Protein productions were induced with the temperature change in E. Coli and analyzed with western blot. RESULTS: The expressed fusion protein can be reacted with both anti-human antibody and COC166-9(AB1 of 6B11). CONCLUSION: The recombinant fusion protein keeps the activities of both components and may be used as tumor vaccine for ovarian cancer.

Immunophenotype of human ovarian malignancies (cystadenocarcinomata and mixed müllerian tumor) established in SCID mice.

Human ovarian malignancies from three different patients (histology: two serous cystadenocarcinomata and one mixed Müllerian tumor, homologous type) were successfully serially transplanted intraperitoneally into severe combined immunodeficient (SCID) mice where the tumor cells spread around the peritoneal cavity. If the ascites derived from cystadenocarcinoma cells engrafted in the female genital tract of the SCID mice, they formed cystic tumors resembling remarkably well the original tumors in the patients. Immunohistochemical analysis revealed that the immunophenotype of the patients' original tumor and those grown in SCID mice were similar in the case of the two cystadenocarcinomata; in addition, the marker expression in general was stable during serial transplantation. If distant metastases occurred in the lungs, they immunophenotypically resembled those grown intraperitoneally. In contrast, the cells derived from the mixed Müllerian tumor shifted during serial transplantation from a spindle cell morphology toward a morphology characterized by cuboidal cells. The transition toward a more epithelial phenotype was accompanied by a changed immunophenotype of the tumor cells which became positive for epithelial cell markers such as carcinoembryonic antigens, CA 19-9 and CA 125. Concurrently with this differentiation, the p53 immunophenotype changed from positive to negative, indicating a further mutation in the p53 gene during serial passages.

Endocrine cells in hepatobiliary cystadenomas and cystadenocarcinomas.

We investigated the distribution of endocrine cells in hepatobiliary cystadenoma (n = 5, two associated with mesenchymal stroma) and cystadenocarcinoma (n = 3) immunohistochemically. In normal livers (n = 20) and livers affected by hepatolithiasis (n = 15) used as controls, endocrine cells revealed by chromogranin immunostaining were located exclusively in normal or proliferating intrahepatic peribiliary glands. In the eight cases of hepatobiliary cystadenoma and cystadenocarcinoma, endocrine cells were present in four cases (50%) (1 cystadenoma, 1 cystadenoma with mesenchymal stroma, and 2 cystadenocarcinomas). Endocrine cells tended to be located beneath and among the columnar epithelial cells. Intrahepatic peribiliary glands were located in the vicinity of cystadenoma or cystadenocarcinoma in six (75%) of the eight cases, and they frequently showed cystic dilatation and contained endocrine cells. Intrahepatic peribiliary glands were located in the vicinity of the endocrine cells in all cystadenomas and cystadenocarcinomas that were positive for endocrine cells. These data show that about 50% of hepatobiliary cystadenomas and cystadenocarcinomas contain endocrine cells and suggest that hepatobiliary cystadenoma and cystadenocarcinoma may originate from intrahepatic peribiliary glands.

Differential diagnosis of ovarian tumors by transvaginal color-pulse Doppler sonography.

To investigate the clinical significance of transvaginal color-pulse Doppler sonography in ovarian tumors, 109 patients were examined at Nagoya University Hospital. Ultrasonographic patterns were classified and the levels of three circulating tumor markers, CA125, CA72-4, and CA19-9, were simultaneously evaluated. In differentiating benign and malignant ovarian tumors, transvaginal color-pulse Doppler and ultrasonographic pattern classification were superior to the tumor markers. Of 49 cases with benign pattern, 45 were benign (91.8%). Of 60 cases with malignant pattern, 24 (40%) were benign and 36 (60%) were malignant or borderline malignant. In this group color-pulse Doppler sonography was the most useful procedure, and sensitivity, specificity, and accuracy were 75.0, 79.2, and 76.7%, respectively. Menopausal status and site of the arterial wave form in the tumor were also important. Transvaginal color-pulse Doppler sonography was a reliable diagnostic method for differentiating ovarian tumors.

Immunomodulation in patients with epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes.

The immunomodulation determined by natural killer cell activity, delayed-type hypersensitivity to purified protein derivative and phytohemagglutin, and phenotypic changes of peripheral blood lymphocytes was characterized in 12 patients with epithelial ovarian cancer who received adoptive transfer of tumor-infiltrating lymphocytes (TILs) after cisplatin-containing chemotherapy (TIL group). As a control, 10 patients with epithelial ovarian cancer who did not receive infusions of TIL were also examined in the same fashion. In the TIL group, peripheral blood lymphocytes showed increased percentages of cells bearing the CD8 antigen, in contrast to stable percentages of CD4 antigen-bearing cells, resulting in a decreased ratio of CD4+ to CD8+ cells. The percentages of CD16 and CD56 antigen-bearing cells also increased in proportion to augmentation of natural killer cell activity against K562 cells. Additionally, with regard to cell-mediated immunity determined by delayed-type hypersensitivity to phytohemagglutin and purified protein derivative, significantly and slightly enlarged erythema was observed 2 and 8 weeks, respectively, after the injection of TILs (phytohemagglutin, P < 0.05; purified protein derivative, not statistically significant). The control group showed no major changes in any of the immunological markers. These results suggest the possibility that the adoptive transfer of TILs induces immunoactivation of cellular immunity and enhances natural killer activity in patients with epithelial ovarian cancer.

[Heterogeneity of the CA125 antigen that coexpresses sialyl Tn and CA19-9 antigens].

High molecular mass glycoproteins detected by the monoclonal antibody OC125 were found in secreted and solubilized materials from the ovarian cancer cell line, HOC-I. The CA125 antigen has been isolated from HOC-I cell extract and conditioned media by perchloric acid precipitation, gel filtration, and OC125 affinity purification. The higher molecular mass complexes (molecular masses were estimated to be > 1,000KDa) was predominantly found in extracts of cells grown in vitro or in ovarian cancer tissues, whereas the lower molecular mass antigen (molecular masses were estimated to be 110-400KDa) was the major component in conditioned media and sera from patients with ovarian cancer. Double determinant enzyme-linked immunosorbent assays were carried out with several antibodies (OC125, NS19-9, TKH-2, B72.3, CC49, MA54, MA61, PC47H) immobilized on a solid phase to bind different epitopes on antigens in clinical samples. Biotinylated OC125 was used as a probe to detect the CA125 antigen that had been bound via different epitopes. When TKH-2 was used to bind the antigen and OC125 used as a probe, the coexpression of CA125/sialyl Tn was observed in 12(22%) of 55 sera from patients with ovarian cancer. In some cases, sialyl Tn or CA19-9 antigens may be present on the CA125 macromolecular complexes.

An unusual evolution of the serum CA 125 level in a ovarian cancer patient.

The usefulness of serum CA 125 measurements in monitoring ovarian cancer has been firmly established in recent years. The CA 125 levels correlate well with tumor status, have a predictive value for second-look operations, indicate responsiveness to chemotherapy, and are a strong independent prognostic factor for survival. We report here a patient with an unusual evolution of the CA 125. The primary treatment consisted of surgery and whole-abdomen radiation followed by adjuvant alkylating agent chemotherapy. Six months after the primary treatment the normal CA 125 level increased to a pathological value during the adjuvant treatment. No tumoral progression could be documented and without changing the medication the value progressively decreased to normal values over a period of 18 months. Actually almost 5 years later the CA 125 remains normal and the patient disease free. After discussion of the different etiologic possibilities the most probably explanation seems to be a radiation-induced peritoneal inflammation. The time interval, the rapid increase, and the progressive decrease of the CA 125 level all correlate well with the histopathological appearance of chronic radiation toxicity.

The role of CA 125 and conventional examinations in diagnosing progressive carcinoma of the ovary.

The clinical significance of the serum marker CA 125 and conventional examinations in diagnosing progressive disease was evaluated in 98 patients. The examinations included CA 125, gynecologic and complete physical examination, abdominal computed tomography (CT), roentgenogram of the chest, second look operation and serum biochemistry profile. Progressive disease occurred in 49 patients and the time to progression was a median of 12 months (range of four to 52 months). At the time of progression, an elevated CA 125 was found in 73 percent of the patients, and in 63 percent of the patients, CA 125 increase preceded clinical progression for a median of four and one-half months (range of 0.5 to 29.5 months). A positive gynecologic examination at progression was found in 67 percent of the patients, physical examination and abdominal CT scan were positive in 30 percent, intervention operation in 14 percent and roentgenogram of the chest in 12 percent of the patients. With the combination of serum CA 125, gynecologic and general physical examination, progressive disease could be diagnosed in 92 percent of the patients. The false-positive rate in the 49 patients with no evidence of disease was 1.6 percent for CA 125, 2.0 percent for gynecologic examination, 4.0 percent for physical examination, 14.0 percent for CT scan and 2.0 percent for roentgenograms of the chest. Serum CA 125 is the most reliable examination to detect progressive disease early. With the combined use of serum CA 125 and the gynecologic and general physical examination, progression of the disease can be detected in about 90 percent of the patients.

[Antitumor effect of PSK and its combined effect with CDDP on ovarian serous adenocarcinoma-bearing nude mice].

Although the antitumor effect of PSK can be increased by potentiating the immune functions of PSK in tumor-bearing hosts, the mechanisms of its action are not fully understood. In this study, we examined the antitumor effect and CDDP combined effect of oral administration of PSK on nude mice bearing a human ovarian cancer cell line (KF cells). 1. PSK was observed to have a significant antitumor effect in tumor-bearing nude mice and subsequently to bring about an increase in the survival rate and prolongation of the life span. 2. The antitumor effect of CDDP was (but not significantly) enhanced by oral administration of PSK and the prolongation of the life span of the tumor-bearing nude mice was obtained. 3. Six weeks after tumor inoculation, no significant natural killer (NK) cell activity in spleen cells from untreated nude mice was observed. However, when PSK (100 mg/kg but not 500 mg/kg) was given every other day, significant NK activity was induced. 4. The serum immunosuppressive acid protein (IAP) value in nude mice treated with PSK alone was significantly higher than that in nude mice treated with a combination of PSK (100 mg/kg) and CDDP. These results suggest that CDDP prevents the increase in serum IAP that occurs when PSK is used and that consequently combinations of PSK and CDDP result in augmentation of antitumor effects.

Lymphocytes isolated from the peritoneal fluid of women with advanced ovarian carcinoma differ significantly from autologous peripheral blood lymphocytes.

The phenotypic and functional analysis of ovarian carcinoma-associated lymphocytes (OCAL), obtained from a group of patients with neoplastic carcinosis, reveals major differences between OCAL and peripheral blood lymphocytes (PBL). Virtually all of the OCAL belong to the T cell lineage, whereas both B and natural killer (NK) cells are virtually absent. NK activity is also significantly lower than that exerted by PBL. Following treatment with rIL-2, lymphokine-activated killer cell activity is poorly inducible in OCAL. In addition, in vitro stimulated OCAL produce low amounts of lymphokines. Clonal analyses reveal a low clonal efficiency, which indicates a severe proliferative defect. T cell clones obtained show peculiar features: the percentage of CD4 and CD8 clones varies greatly in the different samples. Both CD8 and a significant proportion of proliferating CD4+ clones are cytotoxic in a lectin-dependent cytolytic assay. These findings, together with the results obtained from comparative analyses of the peripheral blood of the same group of patients, demonstrate the unique characteristics of OCAL and should be considered in the preparation of protocols for the locoregional immunotherapy of ovarian carcinoma.

Serum and tissue measurements of CA72-4 in ovarian cancer patients.

Serum levels of cancer-associated antigen 72-4 (CA72-4) (tumor-associated glycoprotein 72; TAG-72) from 106 patients with primary ovarian cancer were measured by an immunoradiometric assay employing the monoclonal antibodies (MAbs) B72.3 and CC49. Immunohistochemical localization of TAG-72 was also investigated using immunoperoxidase methodology in conjunction with both light and electron microscopy. In using a cutoff value of 4.0 U/ml for the serum assay, sensitivity of all primary ovarian carcinomas was 63.2% (67.6% of mucinous cystadenocarcinomas and 66.7% of serous cystadenocarcinomas), while specificity of benign ovarian tumors was 91.1%. Diagnostic characteristics of CA125 and CA72-4 have been demonstrated by receiver-operating-characteristics analysis. Although CA125 expressed a remarkable diagnostic efficiency with serous cystadenocarcinoma, it was less efficient with mucinous cystadenocarcinoma. CA72-4, however, was highly detectable for any histological type of ovarian cancer. Immunohistochemical staining with MAbs B72.3 and CC49 in the cytoplasm was stronger than that in the cell membrane in tissues from mucinous cystadenocarcinomas. Also, histological localization of TAG-72 in the microvilli and apical cytoplasmic membrane was demonstrated by electron microscopy using MAb B72.3 and samples of seromucinous cystadenocarcinoma (mixed type). Consequently, TAG-72 was useful for the detection of ovarian carcinoma, especially for monitoring mucinous cystadenocarcinoma, and it is localized in the microvilli and apical cytoplasmic membrane of cystadenocarcinoma cells.

Characterisation and clinical usefulness of CA130 antigen recognised by monoclonal antibodies, 130-22 and 145-9, in ovarian cancers.

A new cancer-associated antigen CA130, recognised by two monoclonal antibodies (moABs) 130-22 and 145-9, was often found to be present at high levels in the sera of patients with ovarian cancer. There was a strong correlation between CA130 and CA125 values. The epitopes recognised by moABs 130-22 and 145-9 were proved to differ from the CA125 epitope, but to exist on the molecule bearing CA125. Unlike OC125, the majority of 130-22/145-9 activity was associated with a much lower molecular mass (less than 200 kDa), indicating that a lower molecular mass immunoreactive determination may be a unique CA130 antigenic determinant within CA125 molecule. Clinical data demonstrate that, (1) elevated levels of CA130 determinant were found in the sera of 91.3% of women with epithelial ovarian cancer, (2) falling or rising levels of CA130 correlated with regression or progression of ovarian cancer in > 95% of cases, (3) normalisation of serum CA130 levels at response does not imply no microscopic residual disease, but CA130 changes during follow-up support the evaluation of recurrence and can be used as a monitoring marker in an individual patient.

The cellular composition in the peritoneal cavity and the cytotoxic function of the peritoneal cells from patients with ovarian cancer; effect of tumor necrosis factor-alpha treatment.

In patients with epithelial ovarian cancer (EOC), the cellular composition in the peritoneal cavity and the functional capacities of the peritoneal cells (PC) are unknown. Especially the peritoneal macrophages (m phi) could play an important role in defense against tumor cells. To study the cellular composition in the peritoneal cavity and the functional capacities of PC, these cells were obtained from three patients with EOC. The PC were immunophenotyped and tested functionally in vitro in a cytotoxicity assay. One of the patients was treated intraperitoneally (i.p.) with a single dose of 0.06 mg/m2 tumor necrosis factor-alpha (TNF-alpha). PC were obtained before the treatment, after 24 h and after 1 week. PC from healthy women undergoing laparoscopic sterilization served as controls. It appeared that patients with EOC have a lower percentage of macrophages (m phi) in the peritoneal cavity than healthy persons. These m phi of patients were also less capable of killing U 937 tumor cells as compared to the peritoneal m phi of control persons. However, in the patient treated i.p. with TNF-alpha the cytotoxic capacities of the peritoneal m phi were strongly improved. The percentage cytotoxicity at an effector to target ratio of 10, increased from 17% to 80%. Thus, the peritoneal m phi in this patient were activated in vivo to a tumoricidal state. These findings indicate that PC in patients with EOC differ from controls, but further investigation is necessary to define the contribution of the disease and/or prior chemotherapy to this defect.

Carcinoembryonic antigen isotypes in tissue sections and loose cyst fluid cells of ovarian neoplasms.

The aim of this study was to establish whether different subsets of ovarian neoplasms express a restricted isotype of carcinoembryonic antigen (CEA) which can be detected in solid tumors and detached cells. Sixty-one cases of mucinous, serous, endometrioid, and Krukenberg tumors were studied by immunohistochemistry using two monoclonal antibodies (MAbs), commercial anti-CEA and D14 with a higher specificity for colorectal adenocarcinomas. The results with both antibodies showed a considerable degree of heterogeneity between cases of nonserous tumors, with a more restrictive pattern observed with the D14 MAb. The proportion of immunostained cells was comparable in tumors and fluids.