Systematic immunohistochemical profiling of 378 brain tumors with 37 antibodies using tissue microarray technology

We performed a systematic immunohistochemical study on 378 brain tumors using 37 antibodies and tissue microarray (TMA) technology. The aim of this study was to find new diagnostic biomarkers using antibodies established in our laboratory. Our TMA consisted of a grid of 1.5-mm cores that were extracted from individual donor blocks. Staining for each antibody was scored using a three-point system. We used hierarchical clustering analysis to interpret these data, which resulted in separation of all the brain tumors into seven groups. Although there were some exceptions, cases with the same histological diagnosis were generally grouped together. We then carried out statistical analyses to find the most useful antibodies for grouping of brain tumors. Ten antibodies [glial fibrillary acidic protein (GFAP), Olig2, vimentin, epithelial membrane antigen (EMA), cytokeratin (AE1/AE3), alpha-internexin, nestin, pinealocytes PP5, aquaporin-4 (AQP4) M13d and AQP4M13e] discriminated between astrocytomas and oligodendroglial tumors. Six antibodies [EMA, AE1/AE3, TUJ1, nestin, neurofilament protein-MH (NF-MH) and perivascular cells GP-1] showed significant differences between high-grade and low-grade gliomas. Our data have revealed new antibodies with potential diagnostic utility (Olig2, PP5, GP-1) and demonstrate that TMA technology is highly useful for evaluating newly established antibodies in brain-tumor research.The original publication is available at www.springerlink.co

Intra-cerebellar schwannoma with various degenerative changes: a case report and a systematic review

[Background] Intra-cranial schwannomas account for less than 8% of brain tumors, among which more than 80% arise from the vestibular nerve. Intra-cerebellar schwannomas are extremely rare. Several cases have been previously reported but without remarkable degenerative changes on histology. [Case presentation] A 61-year-old man presented with worsening disorientation, and an imaging study revealed a cystic lesion (6.5 cm in the largest diameter) in the left hemisphere of the cerebellum accompanied by a mural nodule (2.5 cm) located just inside the skull with enhancement and focal calcification, in addition to hydrocephalus. The lesion was more than 5 mm from the left acoustic nerve. The patient underwent gross total resection. Pathological examination revealed remarkable degenerative changes with various morphological features. Tumor cells were pleomorphic with rich cytoplasm containing numerous eosinophilic granules. Blood vessels and extracellular matrix showed remarkable hyalinization. Immunohistochemical staining revealed that the tumor cells were positive for S-100 protein and negative for Olig2. The tumor was diagnosed as a schwannoma with marked degenerative changes. [Conclusions] The present case is discussed with reference to a systematic review of previous reports of intra-cerebellar schwannoma. Intra-cerebellar schwannoma should be included in the differential diagnosis of cystic lesions with heterogeneous histopathological morphology in the cerebellum

The Feature of Solitary Small Nodular Type of Hepatic Epithelioid Hemangioendothelioma

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor. Preoperative diagnosis of HEHE is difficult because it does not manifest specific symptoms or tumor markers. We report a resected case of small and solitary HEHE. The patient, a 74-year-old man, had undergone surgical resection for left renal cell carcinoma 20 years ago. During follow-up, a tumor approximately 1.3 cm in diameter was detected by computed tomography (CT) at liver segment VIII. It showed isodensity in the arterial phase, low density in the portal venous phase, and homogeneous enhancement in the late phase on CT and magnetic resonance imaging (MRI). We performed hepatic resection of the right hepatic vein drainage area. A pathological diagnosis of HEHE was made. Although small and solitary HEHE is rare, an enhancement pattern in each phase on CT and MRI, using contrast media, can yield clues for the diagnosis of HEHE

Slug, twist, and E-cadherin as immunohistochemical biomarkers in meningeal tumors.

The overexpression of Twist and Slug and subsequent down-regulation of E-cadherin facilitate the acquirement of invasive growth properties in cancer cells. It is unclear which of these molecules are expressed in mesenchymal tumors in the central nervous system. Here, we investigated 10 cases each of hemangiopericytoma, solitary fibrous tumor, meningothelial, fibrous, angiomatous, and atypical meningiomas, and 5 cases of anaplastic meningioma for Slug, Twist, E-cadherin, and N-cadherin immunoexpression. Nuclear Slug expression was observed in 9/10 (90%) hemangiopericytomas and 5/10 (50%) solitary fibrous tumors, but not in any meningiomas, except for 1 case. Similarly, nuclear Twist expression was more extensive in hemangiopericytomas and solitary fibrous tumors than meningiomas. In contrast to Slug and Twist, the positive expression of E-cadherin was observed in 39/45 (87%) meningiomas, but not in any hemangiopericytomas or solitary fibrous tumors (P<0.0001). The fraction of tumor cells expressing E-cadherin in meningeal tumors was negatively correlated to those of Twist (P = 0.004) and Slug (P<0.0001). The overexpression of Slug and Twist with down-regulation of E-cadherin was characteristic findings in hemangiopericytomas and solitary fibrous tumors, but not in meningiomas. The immunohistochemical profiles of the two tumor groups may be useful as diagnostic markers in cases that present a differential diagnosis challenge

Elderly patients aged over 75 years with glioblastoma: Preoperative status and surgical strategies

Background: Standards of care for the elderly with glioblastoma are still unknown, because most studies exclude elderly patients. The effects of preoperative status and surgical strategies on the prognosis for elderly glioblastoma patients were studied. Methods: We defined “elderly” as 75 years or older and retrospectively reviewed 137 patients with glioblastoma, including 31 (22.6%) elderly patients. Relationships between age and clinicopathological variables were investigated. Results: The median overall survival (OS) was 15.8 months in the nonelderly group and 10.8 months in the elderly group (p = 0.02). The median progression-free survival (PFS) was 9.1 months in the nonelderly group and 6.6 months in the elderly group (p = 0.02). Median OS and median PFS had no relationship between low (<70) and high (≥70) Karnofsky performance status (KPS) in the nonelderly group. However, the median OS was significantly longer in the elderly group with high KPS (8.4 months in low KPS, 12.4 months in high KPS; p = 0.003). The median PFS was also significantly longer in the elderly group with high KPS (4.3 months in low KPS, 9.1 months in high KPS; p = 0.04). OS and PFS were significantly longer in the nonelderly group with resection than with biopsy (OS, p = 0.016; PFS, p = 0.039). However, neither OS nor PFS showed any difference with surgical method in the elderly group (OS, p = 0.241; PFS, p = 0.131). Conclusions: Less invasive treatment can be considered as a treatment option in addition to radical resection in glioblastoma patients aged 75 years and older with KPS on admission of less than 70, depending on the general condition

Progression of idiopathic pulmonary fibrosis is associated with silica/silicate inhalation

現在発症原因が不明な肺疾患の特発性肺線維症（IPF）は、シリカやケイ酸塩との関連が疑われている。しかし、一般的なSEM/EDS分析ではケイ素に対する感度が不十分なため、肺葉組織内のケイ素濃度とIPF発症との相関は不明であった。そこで本研究では、SEM/EDSの100倍の感度を有する大気マイクロPIXE分析のX線エネルギースペクトルからケイ素-硫黄比を定量するプログラムを開発し、IPF組織切片とコントロール組織切片の分析に適用したところ、ケイ素-硫黄比の増加が努力肺活量低下等の肺機能悪化と相関があることが明らかとなった