Survivin is a member of a novel protein family of inhibitors of apoptosis, and also plays a role as a potent regulator of mitosis. In semiquantitative Western blot analysis of glioblastomas, survivin ...expression was shown to be a prognostically significant factor. In the present study we investigated the immunohistochemical expression of survivin and its prognostic impact in a large glioblastoma series comprising 104 consecutive adult patients undergoing a first operation for glioblastoma. We analyzed survivin, Ki-67, and topoisomerase-II-alpha expression in paraffin-embedded tissue, and correlated patient age, Karnofsky performance score, vascular pattern and survivin-, Ki-67-, topoisomerase-II-alpha-, and apoptotic indices with patient outcome using univariate and multivariate survival analysis. Survivin was expressed in all glioblastoma samples, and was prominent in a fraction of nuclei of tumor cells and vascular cells. Further, survivin labeled spindle- and chromosomal material of mitotic figures. Faint cytoplasmic expression was also seen. The survivin index showed significant correlation with Ki-67 and Topo-II-alpha indices. On average, 58.85% of Ki-67 and 91.08% of survivin-expressing nuclei co-expressed Ki-67 and survivin. The survivin index did not correlate significantly with overall survival, whereas patient age, Karnofsky performance score, vascular pattern, and Ki-67 and topoisomerase-II-alpha indices were associated with patient outcome. In summary, in glioblastoma, survivin is expressed predominantly in proliferating tumor cell nuclei. In contrast to Ki-67 and topoisomerase-II-alpha, survivin expression does not influence patient outcome. So, in contrast to Ki-67, survivin does not seem to be useful as prognostic factor in the clinical setting.
Secretagogin is a recently described calcium‐binding protein, which is expressed in some neurons of the human brain. In this study we systematically investigated secretagogin expression in 245 ...tumours of the human brain and its coverings using immunohistochemistry. We found focal or widespread secretagogin expression in tumour cells in 1/18 oligoastrocytomas, 1/19 oligodendrogliomas, 2/20 anaplastic oligodendrogliomas, 2/9 ependymomas, 2/11 anaplastic ependymomas, 2/10 glioblastomas, 3/11 gangliogliomas and 1/2 anaplastic gangliogliomas, 10/10 central neurocytomas, 5/10 classic medulloblastomas, 4/5 desmoplastic medulloblastomas, 3/5 large cell/anaplastic medulloblastomas, 3/5 neuroblastomas, 3/10 meningiomas, 2/10 haemangioblastomas, and 13/19 pituitary adenomas. Further, we observed secretagogin expression in endothelial cells in 5/10 meningiomas, 2/5 haemangiopericytomas, and 2/10 haemangioblastomas. We detected no secretagogin expression in fibrillary astrocytoma, pilocytic astrocytoma, DNT, pineocytoma, pineoblastoma, subependymal giant cell astrocytoma (SEGA), atypical teratoid/rhabdoid tumour (AT/RT), or primary central nervous system lymphoma (PCNSL). We conclude that secretagogin is differentially expressed in human neuronal, glial, and embryonal brain tumours, meningial neoplasms and pituitary adenomas. Our findings indicate that secretagogin is involved in the calcium metabolism of tumour cells and endothelial cells in a subset of neoplasms of the brain and its coverings. Anti‐secretagogin immunohistochemistry does not seem to be helpful in most differential diagnostic situations in surgical neuropathology.
We investigated angiogenic patterns and expression of hypoxia-related tissue factors and their prognostic impact in 100 cases of intracranial ependymoma. Angiogenic patterns were evaluated by ...anti-CD34 immunolabeling. Hypoxia-related factors carbonic anhydrase 9 (CA9) and hypoxia-inducible factor 1 alpha (HIF-1alpha) were visualized by immunohistochemistry, and vascular endothelial growth factor (VEGF) mRNA by in situ hybridization. Expression patterns of VEGF and CA9 are similar with regard to distribution (perinecrotic) and extent. HIF-1alpha expression occurs in a significantly smaller fraction of cases and only in a few tumor cells without clear association with necrosis. Expression of VEGF and CA9, but not HIF-1alpha, is associated with a bizarre angiogenic subtype. Combined expression of two or three hypoxia markers (high hypoxia score) associates with presence of necrosis, high proliferation index, bizarre vascular pattern, and increased cellularity. Univariate analysis indicated that patients with high hypoxia score had significantly shorter survival. On multivariate analysis, only proliferation index and extent of resection remained independent predictive factors. We conclude that bizarre vascular pattern, necrosis and high hypoxia score are frequently detectable in intracranial ependymoma, but seem less important for patient outcome than tumor cell proliferation.
Cancer cells bypass replicative senescence, the major barrier to tumor progression, by using telomerase or alternative lengthening of telomeres (ALT) as telomere maintenance mechanisms (TMMs). ...Correlation between ALT and patient survival was demonstrated for high-grade astrocytomas. Transcription from subtelomeres produces telomeric repeat-containing RNA (TERRA), a natural inhibitor of telomerase activity (TA). This led us to evaluate correlations of TERRA and TMM with tumor grade and outcome in astrocytoma patients. SYBR Green real-time reverse transcription-polymerase chain reaction assays for quantitation of total and chromosome 2p and 18p specific TERRA levels were developed. Tumor samples from 46 patients with astrocytoma grade 2 to 4, tissue controls, and cell lines were assessed. TMMs were evaluated by measuring TA and by detecting long telomeres due to ALT. In glioblastoma multiforme (GBM) grade 4, total TERRA levels were similar to cell lines but 14-, 31-, and 313-fold lower compared with grade 3, grade 2, and nonmalignant tissue, respectively. Total TERRA levels differed from chromosomal levels. Low 2p TERRA levels correlated with dense promoter methylation of subtelomeric CpG islands, indicating that TERRA expression in gliomas may be chromosome specific and epigenetically regulated. Total TERRA levels correlated with diagnosis, with low or absent TA and the presence of ALT, and were tentatively associated with favorable patient prognosis in our cohort (
P
= .06). TA and short telomeres identified a subset of GBM with a median survival of only 14.8 months. TERRA and TA may be prognostic in astrocytic tumors.
The assessment of the human epidermal growth factor receptor-2 (HER-2) status has become a routine diagnostic procedure for patients with advanced-stage gastroesophageal adenocarcinoma. The aim of ...this study was to evaluate the possible correlation between the HER-2 status and the ABO blood group. HER-2 status determination and routine ABO typing was performed according to current standards. We evaluated the correlation between the HER-2 status and the ABO and Rhesus (Rh) system in 100 consecutive patients with adenocarcinoma of the upper gastrointestinal tract. There were no significant differences between HER-2 status and ABO and Rh system. Furthermore, no correlation was observed between the HER-2 status and the ABO and Rh type in patients with adenocarcinoma of the upper gastrointestinal tract.
Cardiac troponin T (cTnT) is considered as a specific marker for acute myocardial infarction. Here, we present a case with elevated cTnT, determined by a third-generation assay, without signs of a ...myocardial lesion. Routine investigation of a 66-year-old female patient with indolent B-cell lymphoma revealed increased serum levels of creatine kinase (CK), MB fraction of CK (CK-MB), and cTnT, although she did not complain of cardiac symptoms. Electrocardiographic monitoring, echocardiography, magnetic resonance computed angiography, and percutaneous coronary angiography excluded myocardial damage. However, the close follow-up showed a steady increase of CK-MB and cTnT levels and gradual development of weakness in both thighs. A biopsy of the right quadriceps muscle led to the diagnosis of inclusion body myositis. In contrast to cTnT, cardiac troponin I could not be detected retrospectively in any of her serum samples. These results demonstrate for the first time that cTnT is elevated in patients with inclusion body myositis.
Pleomorphic xanthoastrocytoma (PXA) is an uncommon, usually low-grade, astrocytic tumor. Characteristic histological features include tumor cell pleomorphism and lipidization of tumor cells. Albeit ...prognosis in PXA is generally good, cases with histological signs of anaplasia have been observed. In these cases, the differential diagnosis needs to exclude other malignancies, for example, glioblastoma or malignant fibrous histiocytoma. Immunocytochemical detection of GFAP may support exclusion of non-glial neoplasms resembling PXA. However, GFAP expression in PXA may be faint or focal, although complete lack of GFAP has not been described. A 43-year-old woman was operated on for a left occipital parasagital tumor attached to the dura. Histopathology showed a pleomorphic tumor with moderate mitotic activity and necrosis, lack of GFAP immunoreactivity and ultrastructural detection of premelanosome-like structures. These features led to the tentative diagnosis of amelanotic melanoma, and the patient was irradiated. Three years later she had local tumor recurrence and underwent another operation. The recurrent tumor showed similar plain histology as the first specimen. In contrast, anti-GFAP immunoreactivity was now detectable in pleomorphic tumor cells. Anti-GFAP staining of the first biopsy was repeated using monoclonal and polyclonal antibodies in combination with prolonged tissue pretreatment. Focal GFAP staining of tumor cells was now achieved. We conclude that non-standard GFAP staining protocols may enhance sensitivity and thus lead to detection of a low level of GFAP expression in tumor specimens, in which PXA is considered in the differential diagnosis. This may avoid misleading diagnostic considerations that impact on postoperative patient management.
Abstract
BACKGROUND
Neurosurgical resection is an important treatment option in the multimodal therapy of brain metastases (BM). Perioperative imaging is established in primary brain tumors to assess ...the extent of resection. However, structured guidelines on the use of perioperative imaging for BM patients are so far missing.
METHODS
The European Association of Neuro-Oncology (EANO) Youngsters committee designed a comprehensive questionnaire on the use of perioperative imaging. The survey was distributed to physicians with neuro-oncologic focus via the EANO and the European Association of Neurosurgical Societies (EANS) network.
RESULTS
120 physicians from non-European countries and European countries responded to the survey. 76/120 neurosurgeons, 18/120 radiation oncologists and 17/120 neurologists participated. 89/120 participants worked at academic hospitals and 39/40 participants worked in high patient volume centers as defined by >50 BM cases per year. Local standard operating procedures for perioperative imaging were applied by 94/120 physicians. The preferred preoperative imaging method represented MRI for 112/120 (93.3%) participants. Postsurgical imaging was routinely performed by 106/120 physicians. 77/120 participants indicated MRI as the preferred postoperative imaging method, however, only 71/120 performed postoperative MRI imaging within 72 hours after resection. No correlation of postsurgical MRI and localization at an academic hospital (58/79 73.4% vs. 19/27 70.4%, p>0.05) or patient volume (49/71 69% vs 25/40 62.5%, p>0.05) was evident. The most frequently indicated reason for postsurgical imaging was the assessment of extent of resection as participants indicated to adjust the radiotherapy plan or even considered re-surgery to achieve complete resection. CONCLUSIONS: This EANO survey indicates that preoperative MRI is the preferred imaging technique for the majority of physicians, whereas a high variability of postoperative neuroimaging routines including CT and MRI was observed. International guidelines for perioperative imaging with special focus on postoperative MRI are warranted in order to optimize perioperative treatment modalities for BM patients.
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