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E Müller-Holzner

Publications and source records attributed to E Müller-Holzner.

At least 37 records · Page 2Linked to original sources
PubMed1997

Loss of retinoic acid receptor beta expression in breast cancer and morphologically normal adjacent tissue but not in the normal breast tissue distant from the cancer.

Retinoids and their receptors [retinoic acid receptors (RARs) and retinoid X receptors] play an important role in maintaining the balance between proliferation and apoptosis. Recently, Deng et al. [Science (Washington DC), 274: 2057-2059, 1996] reported a loss of heterozygosity on chromosome 3p24 in breast cancer specimens and the morphologically normal appearing adjacent tissue. The 3p24 locus includes, among other genes, the region coding for RAR-beta. This study was designed to determine whether there are abnormalities in the expression of retinoid receptors in surgical specimens of patients with breast cancer. In 14 patients, transcripts of nuclear retinoid receptors were detected by in situ hybridization in formalin-fixed, paraffin-embedded specimens by means of digoxigenin-labeled riboprobes specific for RAR-alpha, -beta and -gamma. We found RAR-alpha expressed in all specimens, whereas RAR-gamma was expressed in 100% of normal breast tissue but in only 11 of 14 tumorous lesions. RAR-beta was found in all cases of normal breast tissue localized distant from the tumor, but in 13 of 14 cases it was completely absent in the tumor and the morphologically normal appearing tissue adjacent to the tumor. One possibility to explain the suppression of RAR-beta is a mutation in the promoter region. Sequencing the DNA extracted from paraffin-embedded tumor tissue of the corresponding breast cancer specimens, we were not able to detect any mutation in the retinoic acid-responsive element. Our results clearly indicate a crucial role of RAR-beta in the carcinogenesis of breast cancer.

Breast↗
PubMed1997

Parity as an independent prognostic factor in malignant mixed mesodermal tumors of the endometrium.

Malignant mixed mesodermal tumors (MMMT) are the most malignant neoplasms known to occur in the uterus. The most important prognostic factors are the extent of tumor at diagnosis, depth of myometrial invasion, and, as regarded by some authors, the sarcomatous component. We report on a retrospective analysis in 83 patients with MMMT. By univariate analysis survival was dependent on stage, depth of myometrial invasion, kind of therapy, age at menopause, and parity. However, the sarcomatous component did not significantly influence survival. Using the multivariate Cox regression analysis stage and parity or depth of myometrial invasion and parity were found to independently predict prognosis. Despite an interval of more than 20 years from the last childbirth to tumor appearance a beneficial influence of parity on the prognosis of MMMT was identified. This is unique in oncology. Especially patients with more than three children formed a subgroup of long-term survivors. It is interesting to note that parity was found by means of a Cox regression analysis to be statistically independent, and no correlation with other classical prognostic factors was detected.

Aged↗
PubMed1997

Fulminant course of a microinvasive vulvar carcinoma in an immunosuppressed woman.

Iatrogenic immune suppression following renal transplantation is frequently associated with certain neoplasms, including vulvar carcinoma. We describe a patient with a vulvar carcinoma less than 1 mm depth of invasion and less than 3 mm superficial spread 12 years after renal transplantation. A simple vulvectomy was performed but 4 months later disease recurred in the inguinal nodes. The patient died 20 months later with progressive disease in the retroperitoneum and liver metastases.

Adult↗
PubMed1997

High serum levels of soluble CD44 variant isoform v5 are associated with favourable clinical outcome in ovarian cancer.

In 96 ovarian cancer patients, the present study investigates the clinical significance of pretreatment concentrations of soluble CD44 standard (CD44s) and its isoforms v5 and v6 determined in the serum and the ascitic fluid by means of recently developed enzyme-linked immunosorbent assays (ELISAs). Furthermore, CD44 serum concentrations in the ovarian cancer patients were compared with circulating CD44 levels in 50 healthy age-matched female blood donors. Whereas CD44s was found to be higher and CD44v5 to be lower in ovarian cancer patients than healthy control subjects, no statistical difference between the two cohorts was revealed for CD44 isoform v6. In the ascitic fluid samples, variant isoform v5 and v6 were demonstrated at lower concentrations than serum. Multivariate analysis of overall survival demonstrated that a high pretreatment serum level of soluble CD44 isoform v5 is independently associated with favourable clinical outcome in ovarian cancer. When circulating CD44 isoforms were compared with a panel of serum parameters known to be involved in the immunological network, an inverse correlation between serum CD44v5 levels and indicators of cellular immune system activation, such as soluble interleukin 2 receptor, immunostimulatory protein 90K and neopterin, became apparent.

Adult↗
PubMed1996

Different effects of interferons, interleukin-1beta and tumor necrosis factor-alpha in normal (OSE) and malignant human ovarian epithelial cells.

Ovarian cancer arises mostly from the ovarian surface epithelium. The aim of our study was to compare the effects of cytokines in ovarian surface epithelial (OSE) cells and in ovarian carcinoma cells. Proliferation and expression of surface antigens (CA-125 and classes I and II antigens of the major histocompatibility complex [MHC]) were measured in OSE cells obtained from 7 different patients and 7 ovarian carcinoma cell lines. Proliferation of OSE cells remained unaffected by interferon (IFN)-alpha or IFN-gamma, whereas interleukin-1 (IL-1) and tumor necrosis factor (TNF) increased cell growth. Proliferation of ovarian carcinoma cells was reduced by both types of IFN as well as TNF but was not affected by IL-1. Expression of the tumor marker CA-125 was increased by IFN-gamma in ovarian carcinoma cells but not by any other treatment. None of the cytokines affected CA-125 surface expression in OSE cells. Expression of MHC-I was augmented in OSE and in carcinoma cells by both IFNs but not by the other cytokines. Both types of cell were negative for MHC-II, but IFN-gamma induced its expression in both OSE and carcinoma cells. Significant concentrations of the cytokines evaluated here have been measured in blood and follicular fluid by several authors. The different actions of these cytokines in OSE and carcinoma cells could therefore be important in understanding the role of such molecules in the regulation of physiological and pathological processes in the ovary, such as ovulation or malignant proliferation.

Antigens, Neoplasm↗
PubMed1996

Effects of sex- and glucocorticoid steroids on breast cancer cells grown as either multicellular tumor spheroids or monolayers.

The effects of estradiol, medroxyprogesterone acetate (MPA) dexamethasone, dihydrotestosterone and the antihormones 4-OH tamoxifen and RU 38486 were studied in two established breast carcinoma cell lines, the estrogen-sensitive ZR-75-1 and the estrogen-independent BT 20 cells applying two different in vitro systems, spheroid and monolayer cell culture in steroid deprived medium. Growth of ZR-75-1 spheroids was dramatically stimulated by the addition of estradiol, an effect which was neutralized by the simultaneous addition of 4-OH tamoxifen. The antiestrogen alone as well as dihydrotestosterone and MPA reduced ZR-75-1 spheroid growth significantly. While growth of BT 20 spheroids was only transiently inhibited by tamoxifen and dihydrotestosterone, a persistent increase in BT 20 spheroid growth was observed under MPA treatment in a concentration of 1 microM. This effect, although statistically significant, was very moderate. With the exception of this finding, growth effects of the different test compounds were similar in both in vitro systems, tumor spheroids and monolayer cell cultures.

Breast Neoplasms↗
PubMed1996

[Ultrasound morphologic evaluation of the postmenopausal endometrium. A prospective study].

OBJECTIVE: The measurement of the endometrial thickness by means of transvaginal sonography has been discussed as a tool for cancer screening. The aim of the study was to evaluate such a sonomorphological characterization of the endometrium performed by physicians in training. METHODS: A transvaginal sonography was performed in 400 patients before histological examination (dilatation and curettage or hysterectomy). The endometrial thickness measured as double layer and the sonographic patterns were determined. RESULTS: The endometrial thickness correlated with the histological findings: the median thickness was 6 mm for the normal endometrium and increased to 9 mm for polypiform hyperplasias 9.5 for cervical mucous polyps, and to 14 mm for glandular-cystic hyperplasias and carcinomas (p < 0.001 vs. normal). The sonomorphological grading score was also associated with the histology. For the sonomorphological grading, the sensitivity decreased to 80%, but the specificity increased to 62%. CONCLUSIONS: The sonomorphological pattern is superior to the sole determination of the endometrial thickness. This method is practicable under routine conditions performed by physicians in training. However, the specificity of both methods is too low to recommend them for cancer screening.

Aged↗
PubMed1995

Effects of Taxol on choriocarcinoma cells.

OBJECTIVE: Taxol (Bristol-Myers Squibb) (paclitaxel) has been shown to be a potent inhibitor of cell growth for a variety of tumors. We were interested in the antiproliferative efficacy and biologic properties of this novel antineoplastic agent in choriocarcinoma cells. STUDY DESIGN: Human choriocarcinoma cell lines JAR and BeWo were cultured as monolayers and treated with Taxol. RESULTS: Proliferation of JAR and BeWo cells was inhibited by Taxol in a dose-related manner and 1 to 3 nmol/L was sufficient to achieve 50% growth reduction. This effect was accompanied by a marked induction of human chorionic gonadotropin secretion. The effect on human chorionic gonadotropin secretion was dependent on intact protein biosynthesis but not mediated by augmented messenger ribonucleic acid expression. In these choriocarcinoma cells Taxol promoted differentiation as shown by an increase in syncytiotrophoblastic-like cells. Combination of Taxol with either etoposide or methotrexate resulted in antagonistic growth inhibition. CONCLUSION: Taxol is a highly effective antineoplastic agent in choriocarcinoma cells, and clinical trials in refractory disease would therefore be warranted. However, substances other than etoposide or methotrexate should be evaluated for combined treatment. In addition to growth inhibition, differentiation is also induced by Taxol, as shown by increased human chorionic gonadotropin secretion and changed morphologic features.

Antineoplastic Agents, Phytogenic↗
PubMed1995

[Adenofibroma and adenosarcoma of the uterus in young women].

We report on two similar cases of young women with irregular menstrual bleeding. Curettage and biopsy revealed an adenofibroma of the uterus in case 1 (31 yrs) and an uterine adenosarcoma in case 2 (30 yrs). Hysterectomy was subsequently performed in both patients: histological examination of the hysterectomy specimen showed no remnants of the tumour in case 1. There was adenosarcoma tissue in the uterine cavity of case 2 but no myometrial infiltration. The difficulties of differential diagnosis of uterine soft tissue tumours in young women are discussed and the literature is reviewed.

Adenofibroma↗
PubMed1995

[Value of the TAG-72 (CA 72-4) tumor marker in primary diagnosis of ovarian carcinoma. A comparison with the established CA-125 marker].

The value of the TAG-72 (CA 72-4) serum marker in primary diagnosis was investigated in 110 patients with histologically diagnosed ovarian cancer. A reference group consisted of 103 patients with benign pelvic masses. Compared to the well-established CA-125, TAG-72 showed a low sensitivity of 42% in the detection of ovarian cancer. By contrast, when the cut-off level for TAG-72 was set at 6 U/ml, it showed a very high specificity of 99%. When the measurement of TAG-72 was combined to that of CA-125, improvements in both the specificity (as compared to a single CA-125 determination) and the sensitivity (as compared to a single TAG-72 assay) were observed. In such a combined assay, our results suggest that the best predictive value (positive and negative) was obtained if CA-125 is assigned a relatively high cut-off value (65 U/ml) in conjunction with a low cut-off level (3.2 U/ml or 4 U/ml) for TAG-72. In the present study, at threshold values of 65 U/ml respectively, a sensitivity of 86%, a specificity of 83% and a positive and negative predictive value of 85% were obtained. In mucinous carcinomas of the ovary, however, the additional TAG-72 determination did not lead to a better predictive power than did CA-125 measurement alone.

Adenocarcinoma, Clear Cell↗
PubMed1995

IUD-associated pelvic actinomycosis: a report of five cases.

Five cases of intrauterine device (IUD)-associated tuboovarian actinomycosis are presented. The patients' ages ranged from 33 to 49 years and their IUD usage from 2 to 12 years. Clinical features of the cases included stenosis of the sigmoid colon in 4 cases, ureteric or bladder obstruction in two cases, and rectal fistula in a further instance. All patients were successfully treated postoperatively with penicillin or ampicillin. An initial diagnosis of ovarian carcinoma was considered in all cases. Although Actinomyces is difficult to differentiate histopathologically from microorganisms and other substances that cause the Splendore-Hoeppli phenomenon, morphological diagnosis permits a quicker and more practical approach than bacterial cultures in the establishment of postoperative antibiotic treatment. Intraoperative frozen-section diagnosis of an acute inflammatory process permits the surgeon to make an immediate decision in order to avoid extensive surgery when ovarian carcinoma is suspected.

Actinomyces↗
PubMed1994

Immunocytochemical versus biochemical receptor determination in normal and tumorous tissues of the female reproductive tract and the breast.

The development of highly specific and sensitive monoclonal antibodies directed against human estrogen (ER) and progesterone receptors (PR) provides a new approach in precise histochemical receptor location independent of hormone binding. Over the years receptor determination was the domain of the radioligand-binding assay, in which receptors are measured by tritiated ligand and unbound ligand is removed by the dextran-coated charcoal (DCC) procedure. Presented here are the results and experiences obtained by the classic DCC and the immunocytochemical method in the different normal and tumorous tissues of the female reproductive tract and the breast. The results of both methods were compared, and overall concordance of the results was found to vary considerably among the different types of tissue analyzed. Best agreement (86%) was found for PR determination in breast cancer, and the lowest rate of concordance for ER determination in fibrocystic disease of the breast. Special attention was directed toward the heterogeneity of receptor distribution in the specimens examined. In all tissues investigated, ER and PR were located in the nuclei of cells in both paraffin and frozen sections. Staining intensity varied among different cell types and from cell to cell for a single cell type, as well as in tumorous and normal tissues. In breast cancer, randomly scattered single cell receptor positivity was distinguished from focal/clonal positivity. Paraffin-embedded lymph node metastases showed significantly weaker staining as compared with their respective primary tumors. In the normal ovary, the corpus luteum and the stromal layer of the outer cortex were revealed as highly receptive elements for progestins, whereas ER was barely demonstrable in the normal ovary. Benign serous and mucinous ovarian tumors showed opposite ER and PR distribution among the stromal and epithelial components. Of special interest were the highly significant changes in ER and PR content in the stromal and glandular cells of the different layers of the normal endometrium throughout the menstrual cycle.

Breast↗
PubMed1994

Significance of thrombocytosis in patients with epithelial ovarian cancer.

OBJECTIVES: Our objective was to determine the relevance of a preoperative platelet count in ovarian cancer. Special interest was directed to a possible prognostic significance of thrombocytosis in this disease. STUDY DESIGN: Charts of 130 patients with epithelial ovarian cancer were reviewed retrospectively. Survival analyses were performed with the Kaplan-Meier method. Differences in survival were examined according to Mantel and Breslow. Platelet counts were furthermore correlated to other clinical parameters. For this purpose the Spearman rank test and a stepwise logistic regression model were used. Data comparison was accomplished with the Mann-Whitney U test and the chi 2 test. RESULTS: Prevalence of thrombocytosis was 38%. No differences in survival between patients with or without thrombocytosis was found. Volume of ascites and hemoglobin concentrations were independently associated with thrombocytosis (p = 0.002 and p = 0.004, respectively). CONCLUSIONS: Thrombocytosis is not a useful prognostic factor in ovarian cancer. Elevated platelets are predominantly associated with the presence of ascites and marked anemia.

Adult↗
PubMed1994

Uncommon location of persistent ectopic pregnancy following laparoscopic surgery.

BACKGROUND: Laparoscopic surgery has become an important tool in the treatment of tubal pregnancy. Skillful operative technique should prevent tissue spread and thus avoid persistence of ectopic trophoblastic cells. CASE: A laparotomy with complete salpingectomy was performed in a patient with rising serum hCG levels after a previous laparoscopic partial salpingectomy for ampullary tubal pregnancy. The only residual trophoblastic tissue found was an implant in the abdominal wall at the site of auxiliary puncture. CONCLUSION: Extra-abdominal dispersion of active trophoblastic cells may lead to increasing hCG levels, mimicking persistent tubal pregnancy.

Adult↗
PubMed1993

Progesterone receptors in routinely paraffin-embedded primary breast carcinomas and lymph node metastases.

Described here is an immunohistochemical technique using the commercially available monoclonal progesterone receptor (PR) antibody KD 68 in routinely fixed and paraffin-embedded breast carcinomas and lymph node metastases. The authors' technique is compared with several incubation variations. The method applying the primary antibody in a dilution of 1:10 overnight followed by a biotinylated second antibody showed the best results when Triton X-100 was added to the buffer. Using this method, comparison with the results on frozen sections of 34 breast carcinomas yielded a significant concordance of 94%. Correlation between the results on paraffin sections and those obtained by the standard dextran-coated charcoal cytosol assay was 80%. The value of the method for predicting endocrine therapy response was shown in 20 patients. Thus the reliability of the method has been demonstrated and was applied on 151 lymph node metastases and the corresponding primary breast carcinomas from 50 patients. Generally PR content in the metastases was lower than in the primary tumors (p < 0.001). This finding indicates that evaluation of PR in lymph node metastases should be included in the decision for endocrine therapy of breast cancer.

Breast Neoplasms↗
PubMed1993

The prognostic value of nuclear roundness and neopterin in ovarian cancer.

The prognostic value of clinical factors, morphometric features and neopterin, a marker for macrophage activation, was investigated retrospectively in 68 ovarian carcinoma patients. Nuclear roundness was a good predictor of patient survival. About 50% of our patients showed neopterin concentrations above the cut-off level of 275 mumol/mol creatinine. Interestingly, those patients with elevated urinary neopterin concentration, and thus displaying a sign of activation of cell-mediated immunity, had a shorter survival than those with normal concentration. Applying a multivariate Cox regression analysis, the only independent parameters predicting patient survival were FIGO stage, residual disease, nuclear roundness and neopterin.

Adult↗
PubMed1993

Tumor marker CA-125 in tissues of the female reproductive tract and in serum during the normal menstrual cycle.

OBJECTIVE: To further elucidate the origin of the physiological CA-125 amounts that lead to cyclic changes in CA-125 serum levels in normally menstruating women. DESIGN: Fifty-three normal endometria, 13 fallopian tubes, 25 ovaries, and nine isolated corpora lutea were prospectively investigated for their CA-125 content in a sandwich solid-phase RIA and by immunohistochemistry. In addition, endometrial CA-125 tissue content was compared with the actual CA-125 serum levels of the study patients. RESULTS: Cytosolic CA-125 concentrations were 20-fold and twofold higher in the endometrium than those measured in the ovary and the fallopian tube, respectively. Moreover, only in the endometrium did CA-125 content show significant cyclic changes, with the highest concentrations during the early proliferative and middle secretory phase. The lowest tissue concentrations were measured during the early secretory phase. Furthermore, during the early and middle secretory phases cytosolic CA-125 was negatively associated with CA-125 serum levels. In immunohistochemistry, marked distributional changes in OC-125 reactivity were revealed in the basalis and the functionalis throughout the menstrual cycle and the postovulatory loss of CA-125 expression was found to be strongly connected with early secretory transformation of glandular epithelium. CONCLUSION: Our findings indicate that the CA-125 amounts responsible for cyclic changes in serum levels in normally menstruating women seem to be a product of normal endometrium.

Adult↗