p53 Autoantibodies in Patients with Primary Ovarian Cancer Are Associated with Higher Age, Advanced Stage and a Higher Proportion of p53-Positive Tumor Cells

Oncology ◽  
1999 ◽  
Vol 57 (4) ◽  
pp. 324-329 ◽  
Author(s):  
F.D. Vogl ◽  
E. Stickeler ◽  
M. Weyermann ◽  
T. Köhler ◽  
H.-J. Grill ◽  
...  
2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5556-5556
Author(s):  
Pauline Wimberger ◽  
Issam Chebouti ◽  
Jan Dominik Kuhlmann ◽  
Rainer Kimmig ◽  
Eberhart Kuhlisch ◽  
...  

5556 Background: Antiangiogenic treatment in addition to platinum/taxane based chemotherapy was shown to improve progression-free survival in first- and second-line chemotherapy in ovarian cancer patients. Predictive markers for antiangiogenic treatment are of high interest. Therefore we investigated VEGF-receptor (VEGFR) expression as possible biomarker candidate in primary ovarian cancer tissue and its clinical impact. Methods: A total of 82 patients with primary ovarian cancer were enrolled into this study. Primary tumor tissue was analyzed for the expression of VEGFR1, VEGFR2 and VEGFR3 by immunhistochemistry. Moreover, the presence of circulating tumor cells (CTC) in the blood was detected by immunomagnetic enrichment and multiplex reverse transcriptase-polymerase chain reaction (Adnatest Ovarian Cancer, Adnagen). Disseminated tumor cells (DTC) in the BM were identified by immunocytochemistry using the pancytokeratin antibodyA45B/B3 and subsequent automatic detection based on staining and cytomorphology. Results: Positivity for at least one VEGFR was observed in 43% of cases. The positivity rates for VEGFR1, -2 and -3 were 34%, 17% and 27%, respectively. VEGFR-status of the primary tumor neither correlated with established clinicopathogical parameters (age, FIGO-stage, nodal status, grading, histological subtype) nor with the presence of CTC or DTC. In addition, VEGFR-status does not provide prognostic significance in regard to progression-free and overall survival (OS). Nevertheless, a trend was observed that patients, being positive for VEGFR3 at primary diagnosis, were more likely to experience suboptimal debulking (p = 0.074). CTC-positivity after adjuvant therapy significantly correlated with OS, but multivariable analysis showed only residual tumor as prognostic factor for OS. Conclusions: The VEGFR-family, albeit frequently expressed in our patient cohort, provided neither prognostic nor predictive relevance, but could probably be a predictor for debulking efficiency. The implementation of VEGFR-status into future biomarker studies should carefully be considered.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5067-5067
Author(s):  
P. Wimberger ◽  
R. Kimmig ◽  
A. Schulte ◽  
M. E. Scheulen ◽  
S. Kasimir-Bauer

5067 Background: Recent studies in patients (pts) with breast cancer have demonstrated the prognostic significance of disseminated tumor cells (DTC) in the bone marrow (BM) which even can survive high-dose chemotherapy. For ovarian cancer, the impact of chemotherapy on DTC is unknown. Here we evaluated whether first-line chemotherapy with carboplatinum and paclitaxel can eliminate DTC in BM and peripheral blood (PB) of pts with primary ovarian cancer (OC, FIGO IC-IIIC). Methods: PB of 28 pts with OC and bilateral BM aspirates of 18/28 pts were assessed for DTC before and after chemotherapy using density gradient centrifugation and an immunocytochemical cytokeratin (CK) assay with the anti-CK antibody A45-B/B3. Results: We identified CK+ cells in 7/28 blood samples (25%) before therapy with a mean number of 2 cells/20 ml (range 1–3). After chemotherapy, CK+ cells were detected in 3/28 blood samples (11%) with a mean number of 9 cells/20 ml (range 1–18). In 5 out of these 7 CK+ patients prior to therapy, no CK+ cells were found after therapy, a no change and a reduction of DTC could be demonstrated in one patient each. CK+ cells were found in 10/18 BM samples (56%) before therapy with a mean number of 2 cells/9x10E6 BM cells (range 1–7) and in 8/18 BM samples (44%) after therapy with a mean number of 10 cells/9x10E6 BM cells (range 2–35). After chemotherapy, no CK+ cells were found in 6 pts, no change in DTC counts was documented in 2 pts and a significant enhancement of DTC was shown in 6 pts, including 4 pts who had no CK+ cells before chemotherapy. Conclusions: DTC are frequently present in the BM and PB of pts with OC and are not always successfully eliminated after platinum-based chemotherapy. It has to be considered, whether these pts might profit from an additive immunotherapy as already shown by the intraperitoneal application of a trifunctional antibody targeting EpCAM, CD3 and accessory cells (Proc Am Assoc Cancer Res 46: 4260, 2005). No significant financial relationships to disclose.


2016 ◽  
Author(s):  
Issam Chebouti ◽  
Christina Blassl ◽  
Pauline Wimberger ◽  
Hans Neubauer ◽  
Tanja Fehm ◽  
...  

2020 ◽  
Author(s):  
Kung-Chuan Cheng ◽  
Ko-Chao Lee ◽  
Hong-Hwa Chen ◽  
YC Ou

Abstract Background Account for less than 1% of all gastrointestinal tumors, primary appendiceal malignancies are rare and their diagnoses are usually made after exploratory laparotomy. Most of them present with nonspecific symptoms, such as abdominal pain, abdominal fullness and huge pelvic mass, mimicking advanced stage ovarian cancer.Case Presentation We described two menopausal women who were referred to our institution under the impression of advanced stage of primary ovarian cancer. However, both patients were eventually found to have primary appendiceal adenocarcinoma with ovarian metastasis at laparotomy. Initial symptoms, intraoperative finding, pathology finding, and postoperative clinical courses were recorded.Conclusions Comparing with primary ovarian tumor, ovarian metastasis is relatively rare. The clinical picture can be misleading and the differential diagnoses of primary appendiceal cancer should be considered when preoperative workup is planned.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5042-5042
Author(s):  
Pauline Wimberger ◽  
Malgorzata Banys ◽  
Sabine Kasimir-Bauer ◽  
Andreas D. Hartkopf ◽  
Natalia Krawczyk ◽  
...  

5042 Background: Detection of disseminated tumor cells (DTC) in the bone marrow (BM)of breast cancer patients is associated with poor outcome. Recent studies demonstratedthat DTC may serve as a prognostic factor in ovarian cancer.The aim of our study was to evaluate the impact of BM status on survival in a large cohort of ovarian cancer patients. Methods: 365 patients with primary ovarian cancer were included into this three-center prospective study. BM aspirates were collected preoperatively from iliac crest. Disseminatedtumor cells were identified by immunocytochemistry using the pancytokeratin antibodyA45B/B3 and by cytomorphology. Patient outcomes were evaluated using a multivariable Cox regression model. Results: Disseminated tumor cells were detected in 28% of all BM aspirates. The number of CK-positive cells ranged from 1 to 42 per 2x106 mononuclear cells. DTC status did not correlate with any of the established clinicopathogical factors. The overall survival was significantly shorter among DTC-positive patients compared to DTC-negative patients (51 mo, 95% CI: 35 – 67 mo versus 32 mo, 95% CI: 22 – 42 mo; p = 0.003). However, disease-free survival was not related to DTC-positivity. In the multivariable analysis, BM status, FIGO stage, nodal status, resection status and age were independent predictors of reduced overall survival. Interestingly, a subset of DTCs may have stem cell properties since a subset of these cells (128 out of 228 cases) were SOX2 positive, which is an embryonic stem cell marker. Conclusions: Tumor cell dissemination into bone marrow is a common phenomenon in ovarian cancer. DTC detection has the potential to become an important biomarker for prognostication and may be included as a therapeutic target in future concepts.


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