Intracranial extension of adenoid cystic carcinoma: potential involvement of EphA2 expression and epithelial-mesenchymal transition in tumor metastasis: a case report

BACKGROUND: Adenoid cystic carcinoma is a malignant epithelial tumor derived from salivary glands and tends to invade the surrounding structures including nervous system. We present a case of adenoid cystic carcinoma with intracranial extension and propose a novel molecular mechanism of adenoid cystic carcinoma metastasis. CASE PRESENTATION: A 29-year-old Japanese male presented with left trigeminal nerve disturbance. Neuroimaging revealed a tumor located at the right middle cranial and infratemporal fossa. The tumor was removed via a subtemporal extradural and infratemporal fossa approach and histologically diagnosed as adenoid cystic carcinoma. Radiological and operative findings confirmed a perineural spread of the tumor along the mandibular nerve. Immunohistochemical analyses of molecular consequences in this case were performed for better understanding of the biological processes associated with adenoid cystic carcinoma metastasis. First, the neoplastic cells were not immunoreactive for E-cadherin, an epithelial marker, but for vimentin, a mesenchymal marker, suggesting changes in cell phenotype from epithelial to mesenchymal states. Correspondingly, immunoreactivity of transcriptional factors, such as Slug, Twist, matrix metalloproteinase-2 and -9, which are involved in epithelial–mesenchymal transition, were observed. Second, elevated expression of EphA2 receptor, not ephrin-A1, was notable in the neoplastic cells, suggesting morphological changes reminiscent of epithelial–mesenchymal transition and ligand-independent promotion of tumor cell migration and invasion. CONCLUSIONS: We report a case of adenoid cystic carcinoma with perineural spread and provide the first published evidence that EphA2 expression without ephrin-A1 and epithelial–mesenchymal transition might play important roles in adenoid cystic carcinoma progression

Peyer’s Patches in the Terminal Ileum in Ulcerative Colitis: Magnifying Endoscopic Findings

Peyer’s patches (PPs), a major component of the gut-associated lymphoid tissue, serve as important antigen entry sites in mucosal immunity. PPs may play a role in the extension of ulcerative colitis (UC) into the terminal ileum. We sought to clarify the magnified endoscopic findings of the PPs in the terminal ileum of UC patients. Eighteen UC patients underwent magnifying chromoendoscopy before initial treatment to evaluate the follicle-associated epithelium (FAE) on the PPs domes and the surrounding villi. In 8 UC patients, as in healthy controls, the PPs’ domes were slightly elevated, covered with the regular FAE lining, and surrounded by dense and bulky villi; however, in 10 UC patients, the PPs’ domes were irregular, and the surrounding villi were sparse and atrophic. These abnormal findings within the PPs were associated with minimal mucosal lesions but not with backwash ileitis; both electron microscopy and magnifying endoscopy confirmed that these lesions were reversible following remission with prednisolone-mesalazine therapy. Similar to Crohn’s disease patients, UC patients commonly had abnormalities in the FAE on PPs’ domes and the surrounding villi on magnifying endoscopy

Functional Analysis of MeCP2 Mutations Associated with Rett Syndrome Using Transient Expression Systems

レット症候群は生後半年から1歳半ころに発症する重度の精神発達遅滞を伴う疾患で女児の1万人から1万5千人に1人に発症する頻度の高い遺伝子疾患である。この疾患の原因遺伝子が最近MeCP2遺伝子であることが判明した。レット症候群の患者でみられる変異がMeCP2の本来の機能にどのような影響を及ぼすかを理解することは、レット症候群の病態を解明する上での手がかりになる。MeCP2は2つの機能ドメインを持ち、一つはメチル化CpGに結合するメチル化結合ドメイン(MBD)で、もう一つはヒストン脱アセチル化酵素をリクルートするSin3Aと結合する転写抑制ドメイン(TRD)である。報告されている変異の中でミスセンス変異の多くは、この二つのドメイン内でみられ、特にMBD内での変異の割合は多い。MBD内のミスセンス変異のMeCP2機能への影響を把握するため、培養細胞を用いた遺伝子導入発現系を開発して解析を行った

Retention of Capsule Endoscopy at the Site of NSAIDs-induced Intestinal Ulcer ―Lessons to Learn―

A 77-year-old man with a history of non-steroidal anti-inflammatory drugs (NSAID) use was admitted to our hospital due to anemia and hypoalbuminemia. Radioisotope scintigraphy indicated protein loss from the small intestine. The patient underwent capsule endoscopy, which was later found to be retained in the ileum. Double-balloon endoscopy showed multiple strictures with ulcers in the small intestine. The capsule was found in proximal to one of the stenosis, and was removed by doubleballoon enteroscopy. Based on endoscopic findings, NSAID-induced enteritis was diagnosed. Although anemia and hypoalbuminemia improved after discontinuing NSAID, the patient developed ileus and underwent partial resection of the ileum. Multiple diaphragm-like strictures were present in the resected intestine. The current case highlights the importance of screening for intestinal strictures when NSAID ulcer is suspected

Functional Characterisation of MeCP2 Mutatiions Found in Male Patients with X Linked Mental Retardation

MeCP2の遺伝子変異は、Rett症候群以外の疾患の患者でも見つかり、X染色体性の精神発達遅滞を伴う男性患者においても報告された。これらの患者ではMBD内の変異として137番目のGluからGlyと140番目AlaからValのアミノ酸変異が確認された。これらの変異に関して、開発した二つの機能解析系を用いて解析を行ったところ、140番目の変異では、メチル化DNAに対しての転写抑制活性は完全に維持されており、137番目の変異ではわずかに転写抑制活性の低下がみられる程度であった。また、マウス細胞のヘテロクロマチン親和性についても140番と137番目の変異は共に明らかな点状の像を示し、親和性は維持されていた。これらの遺伝性の精神発達遅滞を伴う男性患者でのMeCP2の変異は、その機能への影響がレット症候群の場合と比較して軽度であるため、Rett症候群とは異なる病態を呈する成因となっている可能性が示唆された