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M Untch

Publications and source records attributed to M Untch.

At least 19 recordsLinked to original sources
PubMed2003

Chemosensitivity testing in gynecologic oncology--dream or reality?

Cell culture and animal models have played an essential role in the research of new principles of therapy. Many methods for the individualized testing of therapy sensitivity and resistance have been developed, for example, the clonogenic assay. Presently, the ATP-TCA is commercially available as a testing kit. This review gives an overview of the tumor samples that were tested in the oncologic laboratory in the Department of Obstetrics and Gynecology, Munich Grosshadern between 1993 and 2001. All target parameters show a clear trend in favor of sequential, dose-intensified Epirubicin/Paclitaxel therapy. If this trend remains valid for the total number of patients, a significant impact of this new principle of therapy can be expected. By individualized planning of therapy with ATP-TCA testing, therapy in the individual patient could already be performed by the examination of sensitivity in the preoperative biopsy specimen.

Adenosine Triphosphate↗
PubMed2003

[Shared decision making in breast cancer patients--qualitative study on mutual decision making in breast cancer in a university hospital].

This qualitative study examines doctor-patient interactions and interviews with breast cancer patients referring to shared decision making. The interviews have been evaluated according to the method of grounded theory. Videos of doctor-patient interactions show information and discussions on therapy planning. Breast cancer is a serious, in many cases life-threatening disease. The primary therapy is characterised by confrontation with the diagnosis, fear and hope of the patients and the subsequent treatment. Central themes of the article are the context and implicit assumptions of doctors influencing the shared decision making approach.

Adaptation, Psychological↗
PubMed2003

Breast cancer: monitoring response to neoadjuvant chemotherapy using Tc-99m sestamibi scintimammography.

BACKGROUND: Aim of the study was to assess the value of scintimammography using Tc-99m sestamibi in the evaluation of tumor response to neoadjuvant chemotherapy. MATERIAL ANS METHODS: Results were calculated for 9 patients undergoing neoadjuvant chemotherapy. Scintimammography using 740 MBq Tc-99m sestamibi was performed before, during and after chemotherapy, and sestamibi uptake was scored visually and semiquantitatively to evaluate tumor response. RESULTS: In the case of complete response (n = 3) sestamibi uptake decreased 8 days after beginning neoadjuvant chemotherapy and normalized in the following course. Focal uptake decreased more slowly in patients with partial response (n = 3), who showed clear, persisting tracer accumulation after therapy. The patients without response (n = 3) showed a persisting high tumor activity even after chemotherapy was completed. CONCLUSIONS: The preliminary data suggest that in contrast to other imaging modalities scintimammography appears to yield early information regarding tumor response to neoadjuvant chemotherapy.

Breast↗
PubMed2002

[Detection of disseminated tumor cells in bone marrow--currently of no practical therapeutic value].

Development of metastases in cancer patients is usually due to tumour cells seeding from the primary. These disseminated cells can be detected in blood or bone marrow with the aid of immunocytochemical methods. The clinical significance of this is, however, still controversial. With the aim of determining the prognostic value of disseminated tumour cells, a meta-analysis of 20 publications reporting results based on data collected from a total of 2494 breast cancer patients, was carried out. The outcome of the meta-analysis was that 14 of the 20 studies provided evidence suggesting positive bone marrow findings to be an unfavorable prognostic factor. Five out of twelve studies provided multivariate analytic evidence of an impact of bone marrow status on recurrence-free survival. In five out of twelve studies, a univariate analysis showed a positive bone marrow finding to correlate significantly with overall survival, while a multivariate analysis found such a correlation in only two out of six studies. Owing to a lack of standardization, the results of the individual studies are not directly comparable. Against this background it is too early to say whether the detection of disseminated tumour cells in the bone marrow can be used as a prognostic factor with an impact on therapeutic strategies.

Bone Marrow↗
PubMed2002

Serum CEA and CA 15-3 as prognostic factors in primary breast cancer.

In the present study, we investigated the association of the serum levels of the tumour markers carcinoembryonic antigen and cancer antigen 15-3 with disease free survival and death from disease in 1046 women with breast cancer without metastases at the time of primary diagnosis in relation to age and the established prognostic factors tumour size, lymph node status, histological grading and hormone receptor status. We found that elevated pre-operative serum marker values were correlated with early relapse (cancer antigen 15-3; P=0.0003) and death from disease (carcinoembryonic antigen, cancer antigen 15-3; P=0.0001 both) in univariate analyses. By comparing pre- and post-operative values we found a decline in values post-surgery. In those patients where marker levels of carcinoembryonic antigen decreased more than 33%, a significantly higher risk for relapse and death from disease (both P=0.0001) in univariate analyses was observed. In multivariate analysis this decrease of carcinoembryonic antigen proved to be an independent prognostic factor. The results for cancer antigen 15-3 were comparable to carcinoembryonic antigen in univariate analyses but showed no significance in multivariate analysis. In this study the post-operative decrease of the serum tumour marker carcinoembryonic antigen was a strong independent prognostic factor for disease free survival and death from disease in breast cancer patients.

Breast Neoplasms↗
PubMed2002

[Stereotactic vacuum biopsy in prone and sitting position].

PURPOSE: The purpose of our study was to determine the accuracy of vacuum-assisted biopsy (VB) and to evaluate the side effects of this method depending on the positioning of the patient during the intervention. METHODS: Interventions were performed with the 11-G biopsy needle either in prone position (Mammotest S, Fischer Imaging, USA) on a dedicated table for breast intervention (n = 308) or in upright position with a dedicated digital stereotactic mammography system (Mammomat 3000, Optima, Siemens, Germany). VB was indicated because of indeterminate or suspicious microcalcifications (84.1%) or because of dense lesions (15.9%). All benign results found with VB have been followed up after 6 and 12 months by mammography. All malignant or histological findings discordant to imaging features have been verified by open surgery. RESULTS: Histology after VB offered 215 (64.4%) benign lesions. In neither case a carcinoma developed during follow-up. In 90 (27%) cases malignancy was found with VB. After reexcision the diagnosis of VB was confirmed in 85.6%. In 8.9% of the cases in which VB showed DCIS, histology after open surgery revealed also invasive tumor components. Technical problems occurred in 4 cases. Major side effects developed neither in prone position nor in upright, sitting position of the patient. CONCLUSION: VB is a reliable method with less side effects for the histological evaluation of breast lesions. The accuracy and complications are not depending on the type of stereotactic device or on the patients position. The accuracy of the histological diagnosis achieved with VB can be compared to that of open surgery. The relative high costs of this method may cause a problem. But compared to the costs resulting by open diagnostic surgery this disadvantage is only a relative one.

Adult↗
PubMed2002

[Breast scintigraphy using 99mTc-sestamibi--use and limitations].

AIM: Until now scintimammography did not achieve any definite role in the assessment of breast lesions. Purpose of this study was to elaborate its use as well as the limitations of scintimammography after 500 examinations completed. METHODS: Scintigraphic findings were correlated with the histopathologic outcome of 219 patients, who underwent surgery or biopsy for histopathological confirmation. The results were determined with respect to palpability of the lesion and tumour size. Additionally, a distinct analysis was performed for the patient subpopulation with indeterminate results of previously performed physical examination, mammography, and sonography. RESULTS: Overall sensitivity for scintimammography was 82.1% at a specificity of 87.5%. For palpable lesions sensitivity was 91.7% which was evidently higher as compared to 64.9% for non palpable lesions. For palpable lesions specificity was 81.1% and 88.6% for non palpable lesions. According to tumour size sensitivity ranged between 65.2% for carcinoma with a diameter < 1 cm and 93.7% for carcinoma > 1 cm. In the patients subgroup with indeterminate preliminary diagnosis (n = 143) sensitivity decreased to 71.7% at a specificity of 87.8%. Patients undergoing neoadjuvant chemotherapy showed decreasing sestamibi uptake as early as 8 days after therapy if tumour response was evident. However, small residual invasive tumours in patients with complete remission could not be visualised. CONCLUSION: Scintimammography is neither suited for screening, nor early diagnosis of breast cancer, nor for the further evaluation of small and unclear mammographic findings. Scintimammography should not be used whenever histopathological clarification of a suspicious lesion is necessary. It is useful to further investigate patients with unclear or probably benign findings in physical examination and/or mammography and to monitor tumour response to neoadjuvant chemotherapy.

Breast↗
PubMed2001

Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1.

BACKGROUND: Most patients with lymph node-negative breast cancer are cured by locoregional treatment; however, about 30% relapse. Because traditional histomorphologic and clinical factors fail to identify the high-risk patients who may benefit from adjuvant chemotherapy, other prognostic factors are needed. In a unicenter study, we have found that levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) in the primary tumor are predictive of disease recurrence. Thus, we designed the Chemo N(0) prospective randomized multicenter therapy trial to investigate further whether uPA and PAI-1 are such prognostic factors and whether high-risk patients identified by these factors benefit from adjuvant chemotherapy. After 4.5 years, we present results of the first interim analysis. METHODS: We studied 556 patients with lymph node-negative breast cancer. The median follow-up was 32 months. All patients with low tumor levels of uPA (< or = 3 ng/mg of protein) and of PAI-1 (< or = 14 ng/mg of protein) were observed. Patients with high tumor levels of uPA (> 3 ng/mg of protein) and/or of PAI-1 (> 14 ng/mg of protein) were randomly assigned to combination chemotherapy or subjected to observation only. All statistical tests were two-sided. RESULTS: A total of 241 patients had low levels of uPA and PAI-1, and 315 had elevated levels of uPA and/or PAI-1. The estimated 3-year recurrence rate for patients with low tumor levels of uPA and PAI-1 (low-risk group) was 6.7% (95% confidence interval [CI] = 2.5% to 10.8%). This rate for patients with high tumor levels of uPA and/or PAI-1 (high-risk group) was 14.7% (95% CI = 8.5% to 20.9%) (P = 0.006). First interim analysis suggests that high-risk patients in the chemotherapy group benefit, with a 43.8% lower estimated probability of disease recurrence at 3 years than high-risk patients in the observation group (intention-to-treat analysis: relative risk = 0.56; 95% CI = 0.25 to 1.28), but further follow-up is needed for confirmation. CONCLUSIONS: Using uPA and PAI-1, we have been able to classify about half of the patients with lymph node-negative breast cancer as low risk, for whom adjuvant chemotherapy may be avoided, and half as high risk, who appear to benefit from adjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Nucleosomes in serum of patients with benign and malignant diseases.

High quantities of mono- and oligonucleosomes circulate in the blood of patients with malignant tumors. For their direct quantification in serum, we modified the Cell Death Detection(plus)-ELISA for its application in liquid materials. We examined sera samples from 590 persons, including 418 patients with malignant tumors, 109 patients with benign diseases and 63 healthy persons. We also observed the kinetics of the concentration of nucleosomes in serum samples from 20 patients undergoing chemotherapy and from 16 patients undergoing radiotherapy. Sera of patients with malignant tumors contained considerably higher concentrations of nucleosomes (mean = 350 arbitrary units [AU], median = 190 AU) compared with those of healthy persons (mean = 36 AU, median = 24 AU; p = 0.0001) and patients with benign diseases (mean = 264 AU, median = 146 AU; p = 0.072). Concerning the follow-up investigations, the concentration of nucleosomes in serum increased 24-72 hr after the first application of chemotherapy and 6-24 hr after the start of radiotherapy. A subsequent decrease was often correlated with regression of the tumor. In patients undergoing chemotherapy, an increase in the baseline values of circulating nucleosomes >50%, which were determined before each new therapeutic cycle, was correlated with progression of disease; all patients with disease regression showed a decrease >50% of the baseline values. In patients undergoing radiotherapy, an early decrease of the nucleosomal concentration (< or = 1 day after the initial peak during therapy) to low minimum levels (< or = 100 AU) correlated with good clinical outcome; a late decrease (>1 day) to higher minimum levels (>100 AU) was associated with a worse clinical outcome. Thus, the concentration of nucleosomes in serum might be a useful tool for monitoring the biochemical response during antitumor therapy, especially for the early estimation of therapeutic efficacy.

Cell Death↗
PubMed2001

Her-2/neu analysis in archival tissue samples of human breast cancer: comparison of immunohistochemistry and fluorescence in situ hybridization.

PURPOSE: The objective of our study was to compare the methods used in the literature to analyze HER-2/neu status on archival breast cancer tissue. Therefore, a series of antibodies was evaluated to assess their immunohistochemical (IHC) sensitivity in correlation to gene amplification determined by fluorescence in situ hybridization (FISH). MATERIALS AND METHODS: HER-2/neu overexpression was studied on paraffin sections of 85 invasive breast cancers using a panel of five monoclonal (9G6, 3B5, CB11, TAB250, GSF-HER2) and two polyclonal antibodies (A8010, A0485) in addition to the HercepTest (DAKO, Glostrup, Denmark). HER-2/neu gene amplification was determined by FISH using a dual-color probe (PathVysion; Vysis, Stuttgart-Fasanenhof, Germany). RESULTS: HER-2/neu overexpression was demonstrated in 26% (9G6, TAB250, GSF-HER2), 27% (3B5, CB11), 33% (A8010) and 42% (A0485, HercepTest) of the tumors. FISH on paraffin sections identified gene amplification in 28% of the tumors. Strongly positive IHC results (3+) were always associated with gene amplification. Among the 16 tumors presented with weakly positive IHC results (2+) using the HercepTest, 12 (75%) lacked gene amplification. CONCLUSION: The comparison of IHC and FISH demonstrated an excellent correlation of high-level HER-2/neu overexpression (3+) with gene amplification; ie, FISH does not provide further information in these tumors. However, weakly positive IHC results (2+) obtained with the HercepTest share only a minor association with gene amplification.

Antibodies, Monoclonal↗
PubMed2001

18F-FDG PET and 99mTc-sestamibi scintimammography for monitoring breast cancer response to neoadjuvant chemotherapy: a comparative study.

Presurgical neoadjuvant chemotherapy has shown promise in the treatment of locally advanced breast carcinoma (LABC). Response assessment by clinical examination and mammography is difficult. This study evaluated and compared fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and technetium-99m sestamibi scintimammography (SMM) as potential methods for the early assessment of tumour response to neoadjuvant chemotherapy in patients with LABC. Seven patients underwent PET and SMM [planar and single-photon emission tomography (SPET)] before beginning chemotherapy, after the first and second cycles of chemotherapy and after completing chemotherapy prior to surgery. PET and SMM results were evaluated visually and semi-quantitatively by calculating standardised uptake values (SUV) and tumour/lung ratios in the initial and subsequent studies. The findings were correlated with the initial clinical and mammographic findings and the final histopathological diagnoses. There was a highly significant correlation between SUVmean, SUVmax and the tumour/lung ratio determined with SMM-SPET in the studies performed before and during neoadjuvant chemotherapy. All three patients with complete remission showed decreasing FDG and sestamibi uptake as early as 8 days after therapy. In the presurgical study, increased sestamibi and FDG uptake was no longer evident. Three patients had partial remission with clearly reduced but persisting focal FDG and sestamibi uptake after neoadjuvant therapy. One patient who did not respond to therapy had unchanged intense tracer uptake during chemotherapy that was evident with both techniques. An early decline in glucose metabolism or sestamibi uptake 8 days after beginning therapy did not necessarily predict complete tumour remission in the further course of chemotherapy. On the other hand, increased tracer uptake after the first cycle did not exclude a partial tumour response. After the second chemotherapeutic cycle both techniques were able to distinguish between complete and partial/no response. There was a good correlation between preoperative FDG and sestamibi uptake and the histopathologically determined tumour size. However, small residual invasive tumours in patients with clinically complete remission could not be visualised with either technique. The preliminary data demonstrate that sestamibi SMM is as useful as FDG-PET for the monitoring of tumour response to neoadjuvant chemotherapy.

Adult↗
PubMed2001

HER-2/neu overexpression and in vitro chemosensitivity to CMF and FEC in primary breast cancer.

Available clinical and experimental data on the effect of HER-2/neu overexpression on chemosensitivity are controversial. It was the purpose of this in vitro study to define the association between HER-2/neu overexpression and the sensitivity to the chemotherapeutic drug combinations of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) and 5-fluorouracil, epirubicin and cyclophosphamide (FEC) of breast cancer cells derived from 140 chemotherapy-naïve patients at the time of primary surgery. Both drug combinations were tested at six different concentrations ranging from 6.25-200% peak plasma concentration (PPC). Immunohistochemical detection of HER-2/neu overexpression was performed with the HER-2/neu antibodies, CB11, TAB250 and AO485, in the same tumor specimens. Immunoreactions were determined as negative (0/1+), weakly positive (2+) and strongly positive (3+). However, the antibodies varied in their degrees of sensitivity. Breast cancer samples with strong (3+) HER-2/neu overexpression demonstrated 90% growth inhibition (IC90) at significantly lower PPC values, using the CB11 (p = 0.048), TAB250 (p = 0.007) and AO485 (p < or =0.01) antibodies, and showed 50% growth inhibition (IC50) at significantly lower PPC values, using the CB11 antibody (p = 0.01) compared to their counterparts with lower levels of HER-2/neu expression. When analyzing the group of patients with intermediate and strong HER-2/neu overexpression (2+ and 3+), an association between HER-2/neu overexpression and increased chemosensitivity was seen with the TAB250 (p = 0.044) and AO485 (p = 0.032) antibodies, but not with the CB11 antibody (p =0.8) at the IC90 level. Differences in chemosensitivity between samples with strong HER-2/neu overexpression and those with lower levels were then analyzed separately for CMF and FEC. Both regimens achieved 90% tumor growth inhibition at lower PPC values in samples with strong HER-2/neu overexpression (3+) compared to their counterparts with lower expression levels (AO485 p = 0.011 for CMF, and p = 0.09 for FEC). Cumulative concentration-response plots of tumors responding in vitro with 90% tumor cell inhibition showed a stronger dose dependence for both CMF and FEC among tumor samples with strong HER-2/neu overexpression compared to those with lower levels of expression. In conclusion, the data show that HER-2/neu overexpression was not associated with in vitro drug resistance to CMF or FEC. In contrast, tumors with strong HER-2/neu overexpression demonstrated increased dose-dependent in vitro sensitivity to both the FEC and CMF regimens.

Adult↗
PubMed2001

Drug interactions and cytotoxic effects of paclitaxel in combination with carboplatin, epirubicin, gemcitabine or vinorelbine in breast cancer cell lines and tumor samples.

The purpose of this study was to analyze the drug interactions of paclitaxel (PTX) with epirubicin (EPI), carboplatin (CBDCA), gemcitabine (GEM) and vinorelbine (VIN) in human breast cancer cells and compare the cytotoxic activity of each drug combination in primary breast cancer samples. These experiments were intended to identify the most active agents in combination with PTX, and to provide a preclinical rational for future clinical investigations in breast cancer. Multiple drug effect/combination index (CI) isobologram analysis was applied to combinations of PTX with either CBDCA, EPI, GEM or VIN in MCF-7, MDA-MB-231 and SK-BR-3 human breast cancer cell lines. Drug concentrations were limited to the ranges achievable in humans in vivo, and the drugs were applied simultaneously at fixed molar ratios for each drug combination. Interactions were assessed at multiple effect levels (IC10-IC90). Additionally, the cytotoxic activity of these combinations was assessed in tumor samples of 50 primary breast cancer patients, utilizing the ATP-tumorchemosensitivity assay (ATP-TCA). Drug interactions were shown to be strongly dose-related in the human breast cancer cell lines investigated. At clinically relevant concentrations, CBDCA/PTX demonstrated synergistic (MCF-7) or additive (MDA-MB-231, SK-BR-3) interactions, and EPI/PTX showed additive (SK-BR-3, MCF-7) and antagonistic (MDA-MB-231) interactions. GEM/PTX and VIN/PTX, however, demonstrated antagonism over multiple dose effect levels at clinically relevant drug concentrations in all three cell lines tested. At plasma peak concentrations, EPI/PTX, CBDCA/PTX, GEM/PTX and VIN/PTX achieved > or = 90% tumor growth inhibition in 93, 86, 63 and 50%, respectively, of primary breast cancer samples investigated with the ATP-TCA. Cumulative dose-response plots of primary breast cancer tumor cells responding in vitro with > or = 90% growth inhibition showed a strong dose dependence for both EPI/PTX and CBDCA/PTX. In conclusion, the current data indicate favorable drug interactions for CBDCA/PTX at clinically relevant drug concentrations in breast cancer cells, and demonstrate superior in vitro cytotoxicity of EPI/PTX and CBDCA/PTX compared to GEM/PTX and VIN/PTX in primary breast cancer cultures.

Antineoplastic Agents↗
PubMed2001

Nucleosomes in serum as a marker for cell death.

The concentration of nucleosomes is elevated in blood of patients with diseases which are associated with enhanced cell death. In order to detect these circulating nucleosomes, we used the Cell Death Detection-ELISAplus (CDDE) from Roche Diagnostics (Mannheim, Germany) (details at http:\\biochem.roche.com). For its application in liquid materials we performed various modifications: we introduced a standard curve with nucleosome-rich material, which enabled direct quantification and improved comparability of the values within (CVintraassay:3.0-4.11%) and between several runs (CVinterassay:8.6-13.5%), and tested the analytical specificity of the ELISA. Because of the fast elimination of nucleosomes from circulation and their limited stability, we compared plasma and serum matrix and investigated in detail the pre-analytical handling of serum samples which can considerably influence the test results. Careless venipuncture producing hemolysis, delayed centrifugation and bacterial contamination of the blood samples led to false-positive results; delayed stabilization with EDTA and insufficient storage conditions resulted in false-negative values. At temperatures of -20 degrees C, serum samples which were treated with 10 mM EDTA were stable for at least 6 months. In order to avoid possible interfering factors, we recommend a schedule for the pre-analytical handling of the samples. As the first stage, the possible clinical application was investigated in the sera of 310 persons. Patients with solid tumors (n=220; mean=361 Arbitrary Units (AU)) had considerably higher values than healthy persons (n=50; mean=30 AU; p=0.0001) and patients with inflammatory diseases (n=40; mean= 296 AU; p=0.096). Within the group of patients with tumors, those in advanced stages (UICC 4) showed significantly higher values than those in early stages (UICC 1-3) (p=0.0004).

Anti-Bacterial Agents↗
PubMed2001

Dose-dense and sequential strategies in adjuvant breast cancer therapy.

Several attempts have been made to improve the survival rates of breast cancer patients. The benefit of adjuvant chemotherapy was clearly shown, but the absolute difference of 2% to 11% in overall survival, depending on the patient group, is disappointingly small. In particular, high-risk patients, such as those with > or = 10 involved lymph nodes, extracapsular spread, or vascular invasion, still have an excessive risk of recurrence even after standard adjuvant chemotherapy. To increase the survival rates after adjuvant therapy, new chemotherapeutic agents and new strategies of application are currently being evaluated in clinical trials. Chemotherapy with cyclophosphamide (Cytoxan, Neosar), methotrexate, and fluorouracil (CMF) seems to be safe and effective in patients with breast cancer. In addition, in metastatic patients, dose-intensified chemotherapy is being investigated. The introduction of epirubicin (Ellence), an agent less cardiotoxic and equally active compared to doxorubicin, enabled the escalation of anthracyclines in adjuvant therapy without serious cardiotoxic effects. The combination of dose-intensified chemotherapy and sequential application in the treatment of breast cancer is reviewed.

Antineoplastic Agents↗
PubMed2001

Association of urokinase-type plasminogen activator and its inhibitor with disease progression and prognosis in ovarian cancer.

PURPOSE: Urokinase-type plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor (PAI)-1, have been shown to be related to poor prognosis in a variety of malignant solid tumors. Studies on the prognostic relevance of uPA and PAI-1 in ovarian cancer, however, have been inconclusive. The current study tests the hypothesis that elevated expression of uPA and PAI-1 is associated with prognosis and disease progression. EXPERIMENTAL DESIGN: uPA and PAI-1 were prospectively measured by quantitative ELISA in tumor samples from 103 ovarian cancer patients (82 primary invasive epithelial carcinomas, 9 low malignant potential tumors, and 12 recurrent ovarian carcinomas). RESULTS: uPA but not PAI-1 levels were consistently associated with malignant progression, with levels increased from low malignant potential tumors to primary tumors (uPA, P = 0.04; PAI-1, P = 0.019), from early to advanced disease stages (uPA, P = 0.014; PAI-1, P = 0.23), and from primary to intra-abdominal metastatic tumors (uPA, P = 0.001; PAI-1, P = 0.16). High uPA and PAI-1 levels were associated with residual tumor volumes of >1 cm (P = 0.001 and P = 0.016, respectively). Among invasive International Federation of Gynecologists and Obstetrician stages I-IV tumors, elevated levels of uPA (>5.5 ng/mg) and PAI-I (>18.8 ng/ml) were associated with a shortened progression-free survival (uPA, P = 0.003; PAI-1, P = 0.039) and overall survival (uPA, P = 0.0002; PAI-1, P = 0.007). In multivariate analysis, uPA retained prognostic independence for progression-free survival (P = 0.037) and overall survival (P = 0.006). CONCLUSIONS: These data suggest that the uPA/PAI-1 axis may play an important role in the intra-abdominal spread and reimplantation of ovarian cancer cells. The prognostic relevance of uPA and PAI-1 supports their possible role in the malignant progression of ovarian cancer.

Adult↗