Impact of Resection on Survival of Isocitrate Dehydrogenase 1-Mutated World Health Organization Grade II Astrocytoma After Malignant Progression.

OBJECTIVE: To evaluate the impact of surgical resection and adjuvant treatment on the course of patients after malignant progression of previously treated isocitrate dehydrogenase 1 (IDH1)-mutated World Health Organization (WHO) grade II astrocytoma. METHODS: This retrospective study explored 56 patients undergoing tumor resection for malignant progression after previously treated IDH1-mutated WHO grade II astrocytoma. We analyzed survival after malignant progression, analyzed overall survival (OS), and identified prognostic factors using Kaplan-Meier estimates and log-rank test. RESULTS: By the time of malignant transformation, median age was 44 years, and median Karnofsky Performance Status (KPS) score was 90. Complete resection of contrast-enhancing tissue was achieved in 18 (32.1%) patients. Median survival after re-resection was 33 months (95% confidence interval [CI], 20-46); median OS was 123 months (95% CI, 77-170). Gross total tumor resection, postoperative KPS score ≥80, adjuvant radiochemotherapy, and prior radiotherapy significantly correlated with post-malignant progression survival. CONCLUSIONS: Patients in good clinical condition with malignant progression of previously treated low-grade gliomas should receive aggressive treatment, including re-resection.

Identification of brain- and bone-specific breast cancer metastasis genes.

In breast cancer, metastases are relatively widely distributed, with the most common sites being bone, regional lymph nodes, lung, liver, and brain. The detailed mechanism of organ-specific metastasis is poorly understood. In this study, we initiated a search for genes that are implicated in brain or bone metastasis of primary human breast cancer. We generated gene expression profiles of 18 brain and eight bone metastases derived from primary breast tumors. We identified 73 genes differentially expressed between brain and bone metastases. Visualization of the differential gene expression profiles by correspondence and cluster analyses shows that the metastases clearly separate into two distinct groups as an exact reflection of their site of metastasis. Moreover, the analysis of this gene set in primary breast tumors relapsing to either bone or brain allowed accurate categorization of the tumors according to their metastatic site. The identified genes may prove to be excellent markers to predict the site of metastasis in breast cancer patients and could lead to tailor-made therapy to an individual patient.

New aspects of vulvar cancer: changes in localization and age of onset.

OBJECTIVE: To characterize the changes in incidence, age of disease onset, tumor site and patients characteristics in women with invasive vulvar cancer in a German University Hospital unit over a 28-year period. METHODS: The clinical records for women treated for invasive vulvar cancer from 01/1980 until 06/2007 were analyzed. We performed a retrospective analysis for three 9-year periods: 1/1980 to 02/1989; 3/1989 to 04/1998 and 05/1998 to 06/2007. For each cohort, the number of cases treated, age of disease onset, tumor site and further characteristics were extracted and statistically evaluated. RESULTS: A total of 224 patients with vulvar cancer were identified between 1/1980 and 6/2007. The number and mean age changed significantly over time: between 1/1980 and 02/1989 53 women with a mean age of 65.6 years were treated for invasive vulvar cancer, between 03/1989 and 04/1998 this number increased to 69 women with a mean age of 63.9 years and in the last period, 102 women with a mean age of 57.0 years were treated for vulvar cancer. The total increase was 192%. In the first period 11% of the women were aged 50 years or less compared with over 41% in the third period (p=0.001). Two-third of the tumors women aged<50 years were HPV-positive. Significant changes in the tumor site were observed; from labial position to the region between clitoris and urethra: 37% in the last period compared with 19% in the first period (p>0.05). CONCLUSIONS: Although in the literature the incidence of invasive cancer has been reported to be stable or only minimally increased, the results of this study show that the number of patients presenting with invasive vulvar cancer has doubled within the last three decades at one university hospital unit in Germany, with a nearly 4-time increase in younger patients (+372%) due to HPV high risk infection. The tumor localization changed significantly from the labia to the area between the clitoris and urethra. Assuming that these limited data reflect the general trend in the incidence of HPV-induced vulvar cancer, widely-implemented prophylactic quadrivalent HPV vaccination, which has been proven to be highly effective against anogenital disease, could make an important contribution to the reduction of the risk of vulvar carcinomas in younger women.

A stereotactic device for rabbits based on mandibular and cranial landmarks: technical note.

The authors have developed a stereotactic device for use in rabbits that uses the plane at the base of the mandible combined with cranial sutures as an anatomical reference. The device was developed for a study designed to evaluate catheters for infection prophylaxis, and this required the implantation of silicone catheters along a reproducible trajectory through the lateral ventricle. Cadaver and atlas studies demonstrated consistent spatial relationships between intracranial structures and the surface plane on which the animals were resting during the surgery. This plane is formed by the 2 mandibular angles and the mandibular tip. The authors developed a stainless steel stereotactic device that uses this mandibular plane as well as the coronal and sagittal sutures as spatial references. Operations were performed in 60 animals using the stereotactic device, and postmortem dissections of the animals' brains demonstrated 78.6% accuracy of the trajectory within a tolerance of deviation of 5 degrees , and 94.6% accuracy within a tolerance of 10 degrees . The accuracy of the trajectory of the last 18 consecutively operated animals was constantly within a tolerance of 5 degrees . The device can be autoclaved and, since it is relatively simple and inexpensive to build, the authors manufactured 3 identical frames and used them alternately to operate under sterile conditions. The fast and pain-free head fixation minimized anesthesia-related risks. The authors' experiences suggest that the device is suitable for ventricular punctures and, dependant on the individual requirements of accuracy, other procedures that require "approximate" stereotactic guidance especially when a series of animals need to undergo operations quickly.

Epigenetic silencing of the candidate tumor suppressor gene PROX1 in sporadic breast cancer.

Extensive hypermethylation and consecutive transcriptional silencing of tumorsuppressor genes have been documented in multiple tumor entities including breast cancer. In a microarray based genome-wide methylation analysis of five sporadic breast carcinomas we identified a hypermethylated CpG island within the first intron of the prospero related homeobox gene 1 (PROX1). We, therefore, investigated CpG island methylation of PROX1 in a series of 33 pairs of primary breast cancer and corresponding normal tissue samples by bisulfite sequencing and COBRA analyses. Seventeen of these (52%) breast cancer samples revealed a significant accumulation of methylated CpG sites along with a significant reduction of PROX1 transcription compared to normal breast tissues of the same patients. Frequent methylation was also observed in brain metastases from primary breast cancer (21/37 = 57% of cases). Secondary, we analysed 38 brain metastases of primary breast carcinomas and detected a significantly reduced expression of PROX1 compared to normal breast tissue (p < 0.001) and primary breast carcinomas (p < 0.05), respectively. Additionally, treatment of breast cancer cell lines with demethylating agents could reactivate PROX1 transcription. In summary, we have identified PROX1 as a novel target gene that is hypermethylated and transcriptionally silenced in primary and metastatic breast cancer.