Ganglioglial Differentiation in Medulloblastoma

A case of cerebellar medulloblastoma with clusters of mature ganglion cells and glial cells is described. The patient, a 15 -year -old girl, underwent three operations followed each time by radiation and chemotherapy during the four-year clinical course. Histologically, the ganglion cells were clearly identifiable by their abundant eosino-philic cytoplasm, round nuclei with prominent nucleoli, tigroid granules, and argyrophilic fibrils and axons. Im-munohistochemically, the cells were NSE- and NF positive, and ultrastructurally they contained abundant tubules and filaments, neurosecretory granules and well developed rough endoplasmic reticulum. There were many cells transitional in appearance between primitive cells and mature ganglion cells. The tumor also had many mature yet atypical astrocytes and oligodendrocytes. The exact mechanism of the extensive neuronal and glial maturation of medulloblastoma cells is unclear, but the repetitive surgical interventions, radiation and chemotherapy might have had certain cytostatic effects on rapidly dividing medulloblastoma cells, giving them a chance to mature into postmitotic cells with potential for neuronal and glial differentiation. Acta Pathol Jpn 40: 50–56, 1990.     

Characteristics of histopathological and ultrastructural features of placental villi in pregnant Nepalese women

The placenta is an important functional unit for gas transfer between mother and fetus. The placental membrane, consisting of trophoblast layer interposed between maternal and fetal blood, plays an active role for intensity of respiration, but no morphological evidence has been documented. Until now, it has been reported that fetal growth retardation and increased fetal mortality rate usually could be seen at high altitude. In an attempt to find the cause of high perinatal mortality rate in Nepal, this study was undertaken to examine pathologically about 1000 Himalayan placentas obtained in Nepal and Tibet since 1977, and the results were compared with those of 5500 Japanese placentas at Saitama Medical School since 1990. In this study, characteristics of ultrastructural features of the Nepalese placental villi investigated in recent years are reported. (1) The gross characteristics of placental pathology in the Himalayan group were represented by marked subchorionic fibrin deposits and increased chorionic cysts in contrast to low incidence of intervillous thrombosis compared with those of the Japanese group. (2) As characteristics of histological findings of the placental villi between Himalayan and Japanese groups, the incidence of chorangiosis and chorangioma in the Himalayan group was significantly higher than that in the Japanese group. (3) Accompanying an increase of vasculosyncytial membrane (VSM) in the villi, thickness and separation of basement membrane of the syncytium in addition to increased apoptosis of syncytial cell nuclei were recognized. (4) As characteristic ultrastructural features of chorionic villi of Nepalese placentas, an increase of mitochondria and cystic formation of rough endoplasmic reticulum (rER), in addition to appearance of lamellar bodies similar to alveolar epithelial type II cell in organellae of the syncytium, were observed. These ultrastructural changes of the placental villous capillaries may be ascribed to hypevascularization caused by the chronic hypoxic state. It is, therefore, presumed that trophoblast cells may play an important role for gas transfer mecha-nism under such a hypoxic state at high altitude.     

An inducible short-hairpin RNA vector against osteopontin reduces metastatic potential of human esophageal squamous cell carcinoma in vitro and in vivo.

PURPOSE: To elucidate the clinical significance of osteopontin and the effect of conditional down-regulation of osteopontin in esophageal squamous cell carcinoma (ESCC), we investigated osteopontin expression in tumors and tested an inducible osteopontin-short-hairpin RNA (shRNA) expression vector in an ESCC cell line. EXPERIMENTAL DESIGN: Osteopontin mRNA expression was extracted from gene expression profiles of 23 tumors determined by cDNA microarray and was analyzed. Paraffin sections of 144 tumors were immunohistochemically investigated. Osteopontin protein expression in 34 cell lines was examined by Western blot. A doxycycline-inducible osteopontin-shRNA vector was stably transfected into HSA/c cells to assess the role of osteopontin in cell motility, invasion in vitro, tumor formation, and lymph node metastasis in nude mice. RESULTS: cDNA microarray revealed that high osteopontin mRNA expression was associated with poor survival of ESCC patients (P = 0.029). In immunohistochemistry, osteopontin protein expression was associated with poor prognosis (P < 0.001), distant lymph node metastasis (P = 0.0004), tumor staging (P = 0.027), and histologic grade (P = 0.024). Multivariate analysis showed that osteopontin overexpression was the strongest independent prognostic factor among nine clinicopathologic variables (P < 0.001). Among cell lines tested, 30 had overexpressed osteopontin protein compared with a normal esophageal epithelial cell line. An inducible shRNA vector against osteopontin successfully down-regulated osteopontin expression by 71% to 88% and repressed cell motility by 69% to 97%, cell invasion by 59% to 71%, tumor formation by 56% to 92%, and lymph node metastasis by 50% to 67% in HSA/c cells. CONCLUSIONS: Our findings suggest that osteopontin overexpression may play an important role in progression of ESCC and osteopontin could be a potential target of ESCC therapy.     

Primary pericardial malignant mesothelioma with incomplete endocardial cushion defect; report of a case

Primary pericardial malignant mesothelioma is rare tumor and its prognosis is quite poor due to its late presentation and difficulty of complete resection. We describe a rare case of primary pericardial malignant mesothelioma in a 46-year-old female with incomplete endocardial cushion defect (ECD). Incidentally, we found 2 masses in the pericardial spaces after pericardiectomy. We have successfully removed these 2 masses en bloc and performed a total repair of incomplete ECD. Pathologically, these masses were a primary pericardial malignant mesothelioma. This patient is doing well 4 months after surgery without any evidence of recurrence despite reported poor prognosis of "primary pericardial malignant mesothelioma".     

Heterochromatin Protein 1γ Epigenetically Regulates Cell Differentiation and Exhibits Potential as a Therapeutic Target for Various Types of Cancers

Heterochromatin protein 1 (HP1) is a chromosomal protein that participates in both chromatin packaging and gene silencing. Three HP1 isoforms (α, β, and γ) occur in mammals, but their functional differences are still incompletely understood. In this study, we found that HP1γ levels are decreased during adipocyte differentiation, whereas HP1α and β levels are expressed constitutively during adipogenesis in cultured preadipocyte cells. In addition, ectopic overexpression of HP1γ inhibited adipogenesis. Furthermore, we did not detect any HP1γ protein in the differentiated cells of various normal human tissues. These results suggest that the loss of HP1γ is required for cell differentiation to occur. On the other hand, the methylation levels of lysine 20 (K20) on histone H4 showed a significant correlation with HP1γ expression in both these preadipocyte cells and normal tissue samples. However, all cancer tissues examined were positive for HP1γ but were often negative for trimethylated histone H4 K20. Thus, a dissociation of the correlation between HP1γ expression and histone H4 K20 trimethylation may reflect the malfunction of epigenetic control. Finally, suppression of HP1γ expression restrained cell growth in various cancer-derived cell lines, suggesting that HP1γ may be an effective target for gene therapy against various human cancers. Taken together, our results demonstrate the novel function of HP1γ in the epigenetic regulation of both cell differentiation and cancer development.