Clinical significance of serum DKK-1 in patients with gynecological cancer.

Dickkopf-1 (DKK-1) is a secreted protein involved in embryonic development. Dickkopf-1 is also implicated in osteoporosis, arthritis, and cancer and represents a potential therapeutic target for the treatment of these diseases. Because DKK-1 encodes a secreted protein, we investigated whether the DKK-1 protein is secreted into the sera of patients with gynecological cancer. The levels of DKK-1 protein were assessed by enzyme-linked immunosorbent assay in the sera of 104 patients with gynecological cancer including 36 with ovarian, 40 with cervical, and 28 with endometrial cancers. The serum levels of DKK-1 protein were higher in patients with cervical (314.13 [385.02] pg/mL, P = 0.000) and endometrial (46.95 [21.62] pg/mL, P = 0.000) cancers than in healthy individuals (29.45 [11.86] pg/mL). The serum levels of DKK-1 protein were associated with clinical stage in all patients with gynecological cancer. In patients with cervical cancer, the serum levels of DKK-1 protein were also associated with histological type and lymphatic metastasis. Dickkopf-1 protein detection using enzyme-linked immunosorbent assay as a molecular marker can contribute to the detection and the diagnosis of cervical and endometrial cancers, especially for cervical squamous cell cancer.

A case report of an angiomyxoma in the liver.

Angiomyxomas are uncommon myxoid tumours arising most commonly from the pelvis. A 46-year-old woman with a history of polycystic kidney disease presented asymptomatically for surveillance ultrasonography; changes were noted in the size and morphology of her liver cysts. Subsequent radiological assessment displayed features suspicious of malignancy and a right hemihepatectomy was performed with curative intent. Pathological examination of the resected specimen found histology consistent with an angiomyxoma arising primarily from the liver parenchyma. Follow-up review of the patient has been uneventful with annual imaging showing no evidence of recurrence. Angiomyxomas do not characteristically invade other tissues. However, any liver lesion displaying suspicious features of malignancy should be resected in the absence of disseminated disease.

A study of cyst fluid and plasma carcinoembryonic antigen in patients with cystic ovarian neoplasms.

Cyst fluid and plasma carcinoembryonic antigen (CEA) levels were measured in 11 patients with ovarian cyst-adenocarcinoma and in 16 patients with benign ovarian neoplasms. In patients with ovarian cancer, plasma CEA levels were not elevated above 2.5 ng/ml unless cyst fluid CEA levels were 4 to 16 mu-g/ml. In this series, cystic and plasma CEA levels were elevated most consistently in patients with mucinous ovarian tumors. Furthermore, on the basis of molecular size and immunoreactivity by immunodiffusion, ovarian cancer cyst fluid CEA and colonic cancer CEA had similar immunochemical properties. Consistent with the findings in other neoplasms, follow-up studies showed that plasma CEA levels returned to the normal range between 2 and 12 weeks after surgical excision of the ovarian tumor. It is concluded that plasma CEA is of value in the management of patients with ovarian mucinous cystadenocarcinoma.

[The plasma levels and diagnostic utility of granulocyte colony stimulating factor (G-CSF) and macrophage - colony stimulating factor (M-CSF) in ovarian cancer patients]. / Stezenie i przydatnoscdiagnostyczna czynnika stymulujacego kolonie granulocytarne (G-cSF) i makrofagalne (M-cSF) w osoczu chorych na raka jajnika.

UNLABELLED: G-CSF and M-CSF are of the glycoproteins called colony-stimulating factors (CSFs). Some clinical investigations have shown an autologous production of G-CSF and M-CSF in various human cell lines in vitro and by tumors in vivo. AIM OF STUDY: We have investigated the plasma levels and diagnostic utility of G-CSF M-CSF and commonly accepted tumor marker, such as CA 125 in ovarian cancer patients before surgery and healthy subjects. MATERIAL AND METHODS: We tested 30 patients with ovarian cancer and 30 healthy women (control group). G-CSF and M-CSF were determined using enzyme-linked immunosorbent assay (ELISA), CA 125 was measured by microparticle enzyme immunoassay (MEIA). RESULTS: G-CSF, M-CSF and CA 125 plasma levels were significantly higher in ovarian cancer patients compared to the control group. The diagnostic sensitivity of M-CSF was higher than for G-CSF and CA 125 (57%, 50% i 53%, respectively). The diagnostic specificity was high and equal for all tested parameters (93%). Positive predictive value was higher for M-CSF and CA 125 (equal 89%). Negative predictive value was the highest for M-CSF in comparison to G-C.SF and CA 125 (68%, 65%, 66,7%, respectively). CONCLUSIONS: Our study suggests that especially M-CSF can be clinically useful in diagnostic ovarian cancer, but further investigation and confirmation by a prospective study is necessary.

Low-grade mucinous cystadenocarcinoma in the spleen.

A 69-year-old man with an enlarged spleen, found by computed tomography scan to be multicystic, underwent a splenectomy. Pathological examination revealed a Low-grade mucinous cystadenocarcinoma that was histologically analogous to a mucinous tumor of the ovary. The serum level of tumor markers carcinoembryonic antigen (CEA)and CA19-9 were elevated preoperatively and returned to normal after the operation. In the absence of a primary tumor elsewhere, we considered this tumor to be primary in the spleen, and it was presumed that the tumor arose either from invaginated capsular mesothelium of the spleen or from heterotopic pancreatic or enteric tissue within the spleen.

Prognostic significance of soluble interleukin-2 receptor-alpha in adenocarcinoma of the pancreas.

Soluble interleukin-2-receptor-alpha (sIL-2Ralpha) serum concentrations were examined in chronic pancreatitis patients, patients with cystadenocarcinoma of the pancreas, patients with adenocarcinoma of the pancreas and healthy blood donors. sIL-2Ralpha serum concentrations in pancreatic cancer patients were significantly higher than those of normal control subjects or chronic pancreatitis patients. In patients with adenocarcinoma of the pancreas no significant differences were found between sIL-2Ralpha and tumor size, grading, resectability and lymph node involvement. In Kaplan-Meier regression analysis patients with adenocarcinoma of the pancreas with low sIL-2Ralpha levels (<500 U/ml) lived significantly shorter than patients with sIL-2Ralpha concentrations above 500 U/ml (P < 0.01), suggesting that determination of sIL-2Ralpha serum concentrations could provide additional important information about prognosis.

Relationship between aromatase activity and steroid receptor levels in ovarian tumors from postmenopausal women.

Aromatase activity, as well as steroid receptors, exists in nonfunctional ovarian tumors. Steroid receptor status has been reported to be related to prognosis in ovarian cancer patients. We determined aromatase activity and progesterone receptor (PR) and estrogen receptor (ER) levels in 43 ovarian tumors obtained from postmenopausal women. Aromatase activity was detected in 35 tumors (81%), PR in 21 tumors (49%) and ER in 13 tumors (30%). Eighty-three percent (10/12) of mucinous cystadenoma tissues showed positive PR with high aromatase activity, while 93% (13/14) of malignant tumors showed negative PR and low aromatase activity. Aromatase activity was detected in 95% (20/21) of PR-positive tumors, being greater than in PR-negative tumors (P < 0.002). There was a positive correlation between aromatase activity and PR (rs = 0.49, P < 0.001). However, there was no correlation between aromatase activity and ER. In 17 patients (43%), the serum estradiol level was higher than 30 pg/ml and there was a positive correlation among estradiol, estrone, androstenedione and testosterone. However, serum steroid levels were not correlated with aromatase activity, PR or ER. Aminoglutethimide inhibited aromatase activity of benign and malignant ovarian tumors, uterine myoma, choriocarcinoma cells and purified human placental P-450arom in a similar manner. These results suggest that aromatase activity is correlated with PR in ovarian tumors of postmenopausal women. In addition to steroid receptor status, aromatase activity may be a useful prognostic factor in ovarian cancers.

Lymphocytes in patients with ovarian cancer.

Studies to determine the total number of circulating lymphocytes and their morphologic transformation in the presence of phytohemagglutinin and pokeweed mitogen were carried out in 156 women: 81 who currently had an ovarian cancer or who had had it in the past; 54 normal women; and 21 patients with malignant diseases. The latter two groups served as controls. The total number of circulating lymphocytes is an important cosideration, as there is a significant decrease of lymphocytes in patients with ovarian cancer, a factor with great bearing on prognosis. The lymphoblastic transformation test in the presence of phytohemagglutinin and pokeweed mitogen showed not only significant changes in patients with ovarian cancer but also a correlation with survival at 6 months.

Disseminated intravascular coagulation in gynecologic cancer.

Disturbances in the blood coagulation mechanism are seen by the obstetrician and gynecologist as rare complications of abruptio placentae, retained dead fetus syndrome, amniotic fluid embolism, toxemia, saline amnioinfusion, and septic abortion. Two cases of disseminated intravascular coagulation complicating gynecologic malignancy are presented. Laboratory studies showed thrombocytopenia, hypofibrinogenemia, and increased fibrin degradation products. Derangements of hemostasis in patients with malignancy are discussed from a clinical viewpoint.

Significance of serum tumor markers in patients with carcinoma of the ovary.

A comparison of preoperative serum tumor markers (lactate dehydrogenase, lactate dehydrogenase isoenzymes, alpha-hydroxybutyrate dehydrogenase, alkaline phosphatase, aldolase, leucine aminopeptidase, cholinesterase, erythrocyte sedimentation reaction, carcinoembryonic antigen, alpha-fetoprotein, and beta 2-microglobulin) was made in 76 patients with ovarian or uterine cancer. Sixty-six patients with benign ovarian tumor served as control subjects. From analysis of each tumor marker the greatest positive results were obtained with the markers beta 2-microglobulin (57.1%), lactate dehydrogenase (53.1%), and hydroxybutyrate dehydrogenase (46.2%) for patients with carcinoma of the ovary. The use of these marker combinations in all ovarian cancer patients resulted in a marked increase of the positive rate from 57.1 to 85.2%. In stage I cases, the positive rate increased from 40.6 to 63.6%.

Simultaneous measurement of CA 125, CA 19-9, tissue polypeptide antigen, and immunosuppressive acidic protein to predict recurrence of ovarian cancer.

We studied the utility and limitations of CA 125 for the early diagnosis of recurrence of ovarian cancer and investigated whether the precision of diagnosis could be enhanced by combining CA 125 with other tumor markers. Of 181 patients with epithelial ovarian cancer, 149 were in clinical remission and 35 had developed recurrence. Thirty-four women with recurrence had preoperative CA 125 values of 35 U/mL or more, and 21 (62%) had CA 125 levels of 35 U/mL or more at the time of detection of clinical recurrence. Eleven had levels that remained elevated 3 months before identification of the recurrence. However, in 13 cases CA 125 was below 35 U/mL at the time recurrence was detected. To enhance the efficacy of tumor markers to predict recurrence, patients in whom multiple tumor markers had been measured were studied retrospectively. At the time of clinical recurrence and 3 months earlier, the diagnostic sensitivity of CA 125 alone for recurrence was 64 and 33%, respectively, whereas the sensitivity of a combination of tumor markers (CA 125, CA 19-9, tissue polypeptide antigen, and immunosuppressive acidic protein) was 89 and 66%. Thus, prediction of recurrence of ovarian cancer can be improved by the use of a combination of these tumor markers.

Treatment of cancer patients with a low-density-lipoprotein delivery vehicle containing a cytotoxic drug.

A cytotoxic drug (vincristine, VC) was incorporated into low-density lipoprotein (LDL) and given to cancer patients for the first time by repeated intravenous injection. Individuals presenting with ovarian or endometrial cancer received four or five weekly doses of 1.4 mg/m2 LDL/VC. The uptake of LDL/VC by the adrenal cortex and the liver was minimised by concurrent administration of prednisolone and chenodeoxycholic acid. No febrile, allergic or other reaction attributable to the LDL occurred, and no side effect on haemopoietic, adrenal or liver functions was observed. The neurotoxic side effects commonly seen during VC therapy appeared to be reduced. These results suggest that directed cytotoxic therapy might be achieved in humans through the use of LDL as a carrier. Thus, dose-range and comparative studies using LDL/VC vs VCSO4 are warranted in malignancies in which treatment with the latter drug has been established.

Serum alpha-1-proteinase inhibitor with abnormal properties in ovarian cancer.

It was previously reported that sera from ovarian cancer patients contained abnormal forms of alpha-1-proteinase inhibitor (API) that predicted unresponsiveness to chemotherapy. These molecules were detected by extracting the sera with the fucose-specific lectin, lotus tetragonolobus, and analysing the extracts by electrophoresis. In a new study of ovarian cancer, we report that API cannot be extracted by lotus from fresh sera, unless the specimens are subjected to repeated cycles of freezing and thawing. Furthermore, increases in lotus-extractable API in the pretreated sera are also associated with a poor response to chemotherapy. This would suggest that lotus is extracting the same molecules in both studies. It seems likely that the discrepancy between the two studies is due to the length of time the specimens were stored prior to analysis. We present evidence suggesting that the API extracted by lotus is present in serum as soluble complexes, the detailed composition of which is unclear. The change in the properties of API in cancer may be very important with respect to tumour spread.

Plasma androstenedione and oestrone levels before and after the menopause. II. Non-endocrine ovarian tumours and cysts.

Plasma androstenedione (A) and oestrone (E1) levels were measured by radioimmunoassay in 45 hospitalized patients who had non-endocrine benign or malignant ovarian tumours or cysts. The findings of these measurements were compared with the findings of the mean steroid levels which we determined previously (see previous article) in 135 healthy women, around the menopause, of similar weight. Of the total number of patients, 26 had non-endocrine benign ovarian tumours and cysts and were in the reproductive and pre-menopausal ages. The mean plasma A level was found to be significantly higher than the normal value (P less than 0.001). However, the plasma E1 level was not different from the norm. The remaining 19 patients, all around the menopause, had non-endocrine malignant epithelial ovarian tumours. The mean plasma levels of both A and E1 were found to be significantly higher (P less than 0.001) than the normal values. Since increased plasma A levels are associated with non-endocrine ovarian tumours and cysts, it seems likely that the measurement of plasma A may be used as an endocrine detector of non-endocrine ovarian tumours.

Circulating mucopolysaccharide (mucin) in two adults with metastatic adenocarcinoma. Detection in peripheral blood smear and at autopsy.

We report two cases of circulating mucin that occurred in women with metastatic adenocarcinoma. In both women, mucin was seen on the peripheral blood smear, but no difficulties were encountered in counting blood cells. In one patient, the mucin was grossly visible in the plasma and within phagocytes. Systemic mucin thromboses were detected in the second woman whose death was due to cerebral infarcts from multiple mucin emboli.

Serous papillary cystadenocarcinoma associated with alpha-fetoprotein production.

A 74-year-old woman with a right ovarian tumor had a high level of the serum tumor marker alpha-fetoprotein (AFP). After combination chemotherapy, the serum AFP level decreased significantly. Histopathologic study of surgically excised tumor tissue revealed a serous papillary cystadenocarcinoma. By the indirect immunoperoxidase technique, the AFP was stained in the cytoplasm of the differentiated tumor cells, showing papillary or tubular structures. Serial sections showed that the cells containing PAS-positive substances did not correspond to those producing AFP.

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.

[Amplification of c-myc proto-oncogene in primary tumors, metastases and blood leukocytes of patients with ovarian cancer]. / Amplifikatsiia protoonkogena c-myc v pervichnykh opukholiakh, metastazakh i leikotsitakh krovi bol'nykh rakom iaichnikov.

The structure of DNA sequences homologous to the viral myc oncogene from ovarian tumours, intact tissues and the same patients peripheral blood leukocytes has been studied. The Southern blot analysis of malignant tumour DNA reveals amplification of c-myc protooncogene of 3 from 11 patients. Metastases DNAs of two from those patients also contain multiple copies of c-myc. No myc gene amplification has been detected in 6 examined benign ovarian tumours. The presence of extra copies of myc-related sequences has been shown in two from three DNA samples from peripheral blood leukocytes of patients with ovarian cancer.

[Isolated splenic metastases of cancer of the ovary]. / Métastases spléniques isolées d'un cancer de l'ovaire.

The authors present a case history of a patient whose most recent relapse occurred 7 years after the initial laparotomy carried out for bilateral ovarian stage III cystadenocarcinoma diagnosed by biological follow-up (CA 125) which occurred because of isolated splenic metastases which were identified thanks to ultrasound examination. The literature, which has been searched fails to show a clinical description of a case with metastases localised just to this site. We propose an explanation of the mechanism and an analysis of the methods of follow-up that can be carried out showing that it is useful to use CA 125 as a checK on epithelial tumours of the ovary.

[Tumor markers in the monitoring of ovarian cancer].

This study was carried out to determine the serum level of Ca125, LSA (lipid associated sialic acid) and AGP (alpha acid glycoprotein) in 50 patients with ovarian tumors. Among 30 patients with ovarian cancer, 12 reacted to all three markers, 22 reacted to two markers and 27 reacted to one marker. The sensitivities of LSA and CA125 were 60% and 77%, respectively and the specificities were 85% and 90%. A sensitivity of 87% and a specificity of 95%, when the two markers were used in combination.