Dorothea Fischer

Expression of vitamin D receptor (VDR), cyclooxygenase-2 (COX-2) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in benign and malignant ovarian tissue and 25-hydroxycholecalciferol (25(OH2)D3) and prostaglandin E2 (PGE2) serum level in ovarian cancer patients.

Ovarian carcinomas are associated with increased inflammation which is based upon an up-regulation of inducible cyclooxygenase-2 (COX-2). Moreover, based on our previous published data, the extra-renal vitamin D metabolism seems to be dysregulated in comparison to healthy tissue. In order to gain further insight into the prostaglandin (PG)- and vitamin D-metabolism in ovarian carcinomas, the study aimed to evaluate the expression of the PG metabolising enzymes COX-2 and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) compared to the vitamin D receptor (VDR) in benign and malignant ovarian tissues. Additionally, we determined the 25-hydroxycholecalciferol (25(OH2)D3) serum levels. Expression of VDR, COX-2 and 15-PGDH was determined by Western blot analysis. Serum levels of 25(OH2)D3 and PGE2 were measured by chemiluminescence-based and colorimetric immunoassay. We detected significantly higher expressions of the PG metabolising enzymes 15-PGDH and COX-2 in malignant tissue and PGE2 serum levels were 2-fold higher in tumour patients. Furthermore, we found an inverse correlation to the VDR-expression which was 62.1% lower in malignant tissues compared to that in benign tissues. Surprisingly, we could not detect any differences between the 25(OH2)D3 serum levels in either group (n=20). These data suggest a correlation between PG- and vitamin D-metabolism in ovarian carcinomas.

Diagnosis and treatment options of vulvar cancer: a review

IntroductionVulvar cancer is a rare malignancy in women. However, within the past decade, a distinct increase in the incidence of vulvar intraepithelial neoplasia (VIN) as a precursor lesion, and an increase of vulvar cancer have been reported within Europe and the USA. Surgery is the first choice in treating patients with vulvar cancer, especially in its early stages. In an attempt to decrease the incidence of complications, research was made into modifications of the surgical procedure without compromising the prognosis. The replacement of radical vulvectomy by less wide local excision is one of these modifications. As vulvar cancer is relatively rare, it is possible to give evidence-based treatment recommendations, but usually on a low evidence level. Aim of this paper is to elucidate diagnostics and surgical treatment options in the management of vulvar cancer.Materials and methodsWe searched major databases (i.e. pubmed) with the following selection criteria: vulvar cancer, en bloc resection, triple incision, and sentinel node biopsy.ConclusionsToday, the operative therapy is much less radical and more emphasized on individualized therapeutic concepts. The tendency is to leave the ultraradical surgical options which suffer from high morbidity towards less radical, minimal invasive techniques. Due to the rarity of the disease further studies will have to be performed by international collaborative groups.

Expression of cancer-testis antigen CT7 (MAGE-C1) in breast cancer: An immunohistochemical study with emphasis on prognostic utility

High expression of the cancer-testis antigen CT7, also referred to as MAGE-C1, has been recently described in a variety of malignant tumors, including breast carcinoma. To our knowledge, no data concerning the prognostic utility of CT7 expression in breast cancer are available. In this retrospective study, we evaluated the relationship between CT7 immunoreactivity and clinicopathological parameters as well as relapse-free survival (RFS) and metastasis-free survival (MFS) of 124 women with invasive breast cancer. A positive CT7 status, defined as immunoreactivity in more than 50% of tumor cells, was found in 18% of cases and correlated significantly with high tumor grade (p=0.004), but with no other clinicopathological parameter. In a univariate analysis, CT7 status showed an association with RFS by trend (p=0.107; relative risk [RR]: 1.85) and a significant association with MFS (p=0.043; RR: 2.02). In a multivariate analysis, tumor grade, stage, nodal status, angioinvasion, HER2 expression as well as estrogen and progesterone receptor expression were identified as significant independent prognostic factors of RFS and/or MFS. In this respect, CT7 expression showed a weak, statistically not significant trend towards an independent prognostic relevance concerning prediction of MFS (p=0.147; RR: 1.95). Our data suggest that estimation of CT7 immunoreactivity is of limited prognostic usefulness in breast cancer. It may provide additional information concerning assessment of MFS in selected cases.

Multiple sclerosis and pregnancy: what does the patient think? a questionnaire study.

BackgroundMultiple Sclerosis (MS) is primarily a disease of women in their childbearing years. Pregnancy and puerperium have opposite effects on the course of the disease. Nevertheless, no studies have been carried out yet on the level of information among female MS-patients regarding the interaction between MS and pregnancy.FindingsDemographic data, clinical features of MS, course of MS during pregnancy and puerperium as well as knowledge concerning MS and pregnancy were evaluated by means of a questionnaire in 154 female MS-patients. The level of information was significantly higher (p < 0.001) in women who had been pregnant in the past with the diagnosis MS known at this point of time. Furthermore patients reported about a lower frequency of relapses during pregnancy and a higher frequency of relapses in the first six months after giving birth.ConclusionsThe findings illustrate a lack of knowledge in female MS-patients concerning the interactions of MS and pregnancy. In order to make their own independent decision based on scientific facts known to date, female MS-patients need to be better informed on issues regarding MS and pregnancy.

Expression of splice variants of 1α-hydroxylase in mcf-7 breast cancer cells

Abstract 1,25-Dihydroxyvitamin D 3 (calcitriol) is the most active natural metabolite of Vitamin D 3 . It has strong antiproliferative and differentiating effects on various cell types including breast cancer cells. 25-Hydroxyvitamin D 3 -1α-hydroxylase (1α-hydroxylase, CYP27B1) is one of the key enzymes in the formation of calcitriol. It has been found in breast cancer cells suggesting an autocrine regulation of formation of calcitriol in these cells. Alternative splicing of the encoding genes for this enzyme can possibly play a role in regulating the enzyme level and can explain tissue specific variations of 1α-hydroxylase activity. Splice variants containing intron 1 may encode for truncated proteins with deletion of protein domains which are essential for its enzymatic activity. In order to obtain more information on the abundance of 1α-hydroxylase splice variants, we performed a highly specific nested touchdown PCR in MCF-7 cells. The full-length sequence of 1α-hydroxylase and two different splice variants of this enzyme containing intron 1 were isolated. By Western blot technique we then confirmed the protein products of the full-length enzyme and its splice variants. We hypothesize that that the expression of splice variants can lead to a quantitatively lower expression of the mRNA of the full-length enzyme. The abundance of less active 1α-hydroxylase protein variants can alter the local synthesis of calcitriol in the cells and may explain variations of enzymatic activity in different cells and tissues.

Benefits of the quality assured double and arbitration reading of mammograms in the early diagnosis of breast cancer in symptomatic women

ObjectivesTo address the benefits of double and arbitration reading regarding tumour detection rates, percentage of in situ tumours, and number (of patients) needed to send for expert reading (number needed to treat; NNT) for one additional tumour finding.MethodsQuaMaDi is a quality assured breast cancer diagnosis programme; with two-view mammography (craniocaudal, mediolateral oblique) and, in case of breast density ACR 3 or 4, routine ultrasound imaging; and with independent double reading of all images. A consecutive sample of symptomatic women, i.e. women at risk for breast cancer, women aged 70 and above, and/or women with preceding BI-RADS III findings, was analysed.Results28,558 mammograms were performed (mean age of women: 57.3 [standard deviation: 12.3] years). Discordant findings were present in 3,837 double readings and were sent for arbitration reading. After histopathological assessment, 52 carcinomas were found (thereof 32% in situ). These carcinomas accounted for 1.8 tumours per 1,000 examinations in the total cohort and increased the tumour detection rate up to 16.4/1,000. The NNT in discordant cases was 74.ConclusionDouble and arbitration reading appears to be a useful tool to ensure the quality of early detection of breast lesions in symptomatic women during indication-based, standardised mammography.Key Points• Quality assured breast cancer diagnosis is feasible outside organised screening structures.• Double and arbitration reading is beneficial for populations ineligible for screening.• Double and arbitration reading increases the tumour detection rate.• Double and arbitration reading increases the percentage of in situ cancers.

Prognostic factors for survival and intracerebral control after irradiation for brain metastases from gynecological cancer.

OBJECTIVE The most appropriate treatment for the individual patient with brain metastases from gynecological cancer is unclear. Most of these patients receive whole-brain radiotherapy (WBRT) alone. Prognostic factors predicting the outcomes of these patients may guide the physician to select the appropriate treatment regimen for the individual patient. METHODS The data of 42 patients with brain metastases from gynecological cancer treated with WBRT alone were retrospectively analyzed. Six potential prognostic factors were evaluated for survival and intracerebral control including WBRT regimen, age, Karnofsky performance score (KPS), primary tumor type, number of brain metastases, and extracranial metastases at the time of WBRT. RESULTS On univariate analysis, improved survival was associated with KPS > or = 70 (P<0.001), <4 brain metastases (P=0.033), and lack of extracranial metastases (P=0.008). On multivariate analysis, KPS maintained significance (P<0.001). On univariate analysis, improved intracerebral control was associated with KPS > or = 70 (P=0.003). KPS was also significant in the multivariate analysis (P=0.007). CONCLUSIONS KPS was the most important predictor for both survival and intracerebral control. For patients with a KPS <70, a short-course of WBRT appears appropriate. For patients with a KPS > or = 70, more aggressive treatment regimens including longer courses of WBRT, resection or radiosurgery should be seriously considered.

Metastasized hemangiopericytoma of the breast: a rare case

Sarcoma of the mammary glands is extremely rare. Liposarcoma, leiomyosarcoma, rhabdomyosarcoma, as well as hemangiopericytoma, are part of the soft tissue sarcoma group. Little is known about the progress, prognosis and dissemination of this infrequent tumor entity. We present the case of a woman, who received primary diagnosis of a malignant hemangiopericytoma of the left breast. She underwent a mastectomy with an axillary lymph node sampling (stage pT3 pN0 cM0), as adjuvant therapy was not mandatory. Eight months after diagnosis, the patient presented with lumbar back pain, gluteal pain and right accentuated adynamia in both legs because of a disseminated osseous metastasis. Diagnostic investigation presented a cerebral, pulmonary, cutaneous, hepatic and pleural metastatic disease. Two months after initiation of chemotherapy the patient died. Diagnostic criteria and treatment principles in the metastatic situation are presented in addition to the literature to give a review about this rare malignancy.

A New Scoring Tool to Assess Overall Survival in Patients With Intracerebral Metastases From Gynecological Cancers

Objective This study aimed to facilitate individualized treatment strategies for intracerebral metastases from gynecological cancers by creating a specific overall survival (OS) score. Methods/Materials Fifty-six patients irradiated for cerebral metastases from gynecological cancers were included. Eleven factors were retrospectively analyzed for OS: age, Eastern Cooperative Oncology Group (ECOG) performance score, cancer type, histology, histologic grading, initial stage, number of lesions, extracerebral metastases, time between cancer diagnosis and brain metastases treatment, recursive partitioning analysis class, and type of treatment. Independent predictors of OS were incorporated in the score (better OS, 1 point; worse OS, 0 points). Results On Cox proportional hazards analysis, performance score (hazards ratio, 1.98; 95% confidence interval, 1.30–3.23; P = 0.001), no extracerebral metastases (3.34; 1.46–8.96; P = 0.003), and recursive partitioning analysis class 1 (3.27; 1.97–5.65; P < 0.001) were significant. The following points were assigned: ECOG score 1 to 2 = 1 point, ECOG score 3 to 4 = 0 points, no extracerebral metastases = 1 point, extracerebral metastases = 0 points. Sum scores were 0 (n = 32), 1 (n = 15), or 2 points (n = 9). Six-month OS rates were 6%, 67%, and 100%, respectively (P < 0.001). Conclusions A predictive tool including 3 groups with significantly different OS probabilities was designed for patients with cerebral metastases from gynecological cancers. This tool will aid in choosing individual treatments.

Early-Onset Breast Cancer: Effect of Diagnosis and Therapy on Fertility Concerns, Endocrine System, and Sexuality of Young Mothers in Germany

Background: The purpose of this study was to analyze the effect of breast cancer therapy on fertility concerns and sexuality of young mothers with breast cancer in Germany. Methods: During a mother-child rehabilitation program, 1,191 young mothers with locoregional primary breast cancer, treated between 2006 and 2014, were recruited. Data included sociodemographic data, TNM stage, tumor biology, therapies, and patient-reported outcomes such as sexuality and fertility concerns. Results: The mean age at diagnosis was 40 years. Approximately a quarter of the patients stated that family planning had not been completed at the time of diagnosis. Nearly half of all patients had been informed as to how treatment could affect fertility, but counseling at a specialized fertility center was offered to only 13%. Of all patients, 4% took a consultation and 2% underwent fertility preservation procedures. Conclusion: Our study indicates that only a minority of patients is referred to fertility centers although family planning is incomplete at the time of diagnosis in about 25% of young women with breast cancer. Thus, these patients should not only be informed about the effects of treatment on fertility and sexuality, but should be referred to a fertility center.