Objective: To investigate immunohistochemical patterns of CXorf67 and H3K27me3 proteins in central nervous system germ cell tumors (GCTs) and to assess their values in both diagnosis and differential diagnosis. Methods: A total of 370 cases of central nervous system GCTs were collected from 2013 to 2020 at Huashan Hospital of Fudan University, Shanghai, China. The expression of CXorf67, H3K27me3 and commonly-used GCT markers including OCT4, PLAP, CD117, D2-40, and CD30 by immunohistochemistry (EnVision method) was examined in different subtypes of central nervous system GCTs. The sensitivity and specificity of each marker were compared by contingency table and area under receiver operating characteristic (ROC) curve. Results: Of the 370 cases there were 282 males and 88 females with a mean age of 19 years and a median age of 17 years (range, 2-57 years). Among the GCTs with germinoma, the proportions of male patients and the patients with GCT located in sellar region were both higher than those of GCTs without germinoma (P<0.05), respectively. CXorf67 was present in the nuclei of germinoma and normal germ cells, but not in other subtypes of GCT. H3K27me3 was negative in germinoma, but positive in the nuclei of surrounding normal cells and GCTs other than germinoma. In the 283 GCTs with germinoma components, the expression rate of CXorf67 was 90.5% (256/283), but no cases were positive for H3K27me3. There was also an inverse correlation between them (r²=-0.831, P<0.01). The expression rates of PLAP, OCT4, CD117 and D2-40 were 81.2% (231/283), 89.4% (253/283), 73.9% (209/283) and 88.3% (250/283), respectively. In 63 mixed GCTs with germinoma components, the expression rate of CXorf67 was 84.1% (53/63), while all cases were negative for H3K27me3. The expression rates of PLAP, OCT4, CD117 and D2-40 were 79.4% (50/63), 79.4% (50/63), 66.7% (42/63) and 87.3% (55/63), respectively. The 6 markers with largest area under ROC curve in ranking order were H3K27me3, CXorf67, D2-40, OCT4, PLAP and CD117 (P<0.05). Conclusions: CXorf67 and H3K27me3 have high sensitivity and high specificity in diagnosing germinoma. There is a significant inverse correlation between them. Therefore, they can both be used as new specific immunohistochemical markers for the diagnosis of GCTs.
Adolescent ; Adult ; Brain Neoplasms/pathology* ; Central Nervous System/pathology* ; Central Nervous System Neoplasms/metabolism* ; Child ; Child, Preschool ; China ; Female ; Germinoma/pathology* ; Histones ; Humans ; Male ; Middle Aged ; Neoplasms, Germ Cell and Embryonal/diagnosis* ; Oncogene Proteins ; Transcription Factors/metabolism* ; Young Adult

No abstract available.
Antineoplastic Agents/*therapeutic use ; Benzamides/*therapeutic use ; Central Nervous System Neoplasms/*diagnosis ; Fusion Proteins, bcr-abl/genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy ; Leukocytes/metabolism/pathology ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Piperazines/*therapeutic use ; Pyrimidines/*therapeutic use

Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke's cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent.
Adenoma/*pathology ; Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Central Nervous System Cysts/pathology ; Child ; Female ; Growth Hormone/metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Pituitary Neoplasms/*pathology ; Prolactin/metabolism ; Recurrence ; Sex Factors ; Young Adult

Adenocarcinoma ; metabolism ; Adenoma ; metabolism ; Breast Neoplasms ; metabolism ; Carcinoma, Papillary ; metabolism ; Carcinoma, Small Cell ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; Central Nervous System Neoplasms ; metabolism ; Diagnosis, Differential ; Digestive System Neoplasms ; metabolism ; Female ; Genital Neoplasms, Female ; metabolism ; Humans ; Immunohistochemistry ; Kidney Neoplasms ; metabolism ; Liver Neoplasms ; metabolism ; Lung Neoplasms ; metabolism ; Neuroendocrine Tumors ; metabolism ; Nuclear Proteins ; metabolism ; Pituitary Neoplasms ; metabolism ; Small Cell Lung Carcinoma ; metabolism ; Thyroid Neoplasms ; metabolism ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism

Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Astrocytoma ; metabolism ; pathology ; CD3 Complex ; metabolism ; Central Nervous System ; metabolism ; pathology ; Central Nervous System Neoplasms ; metabolism ; pathology ; Demyelinating Diseases ; diagnosis ; metabolism ; pathology ; Diagnosis, Differential ; Glial Fibrillary Acidic Protein ; metabolism ; Humans ; Lymphoma ; metabolism ; pathology ; Magnetic Resonance Imaging

OBJECTIVETo investigate the glycolytic phenotype of SHG44 human glioma cells under hypoxic conditions and the association between cell proliferation and apoptosis and the metabolic status.

METHODSAn in vitro hypoxic cell model was established in SHG44 cells using CoCl2. Real-time PCR and Western blotting were used to assess the expressions of hypoxia-inducible factor-1α (HIF-1α) and the enzymes involved in glycolysis including PDK1, PKM2, and LDHA. Intracellular ATP levels were measured by bioluminescence assay to assess the energy metabolic status of SHG44 cells. The viability and apoptosis of the cells were examined using MTT assay and flow cytometry, respectively.

RESULTSThe cells in hypoxic culture showed obviously increased expressions of HIF-1α, LDHA, PDK1, and PKM2 at both the mRNA and protein levels as compared to those in normal cell culture. Hypoxia of the cells also resulted in a lowered cell proliferative activity and an increased apoptosis rate with lowered intracellular ATP concentrations and elevated mitochondrial membrane potential.

CONCLUSIONHypoxia can induce a glycolytic phenotype of tumor cells. The sensitivity of tumor cells to hypoxia-induced cell death is directly correlated with their metabolic status.

Adenosine Triphosphate ; metabolism ; Apoptosis ; Carrier Proteins ; metabolism ; Cell Hypoxia ; Cell Line, Tumor ; Cell Proliferation ; Central Nervous System Neoplasms ; metabolism ; pathology ; Glioma ; metabolism ; pathology ; Glycolysis ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Membrane Potential, Mitochondrial ; Membrane Proteins ; metabolism ; Protein-Serine-Threonine Kinases ; metabolism ; Thyroid Hormones ; metabolism

This study was aimed to investigate the expression of osteopontin (OPN) in central nervous system leukemia (CNSL) and to understand its clinical significance. The expression level of OPN in serum of 62 pediatric patients (22 cases of CNSL, 20 cases of acute leukemia without extramedullary infiltration and 20 cases of nontumor patients) and 19 cases of CNSL with complete remission (CR)were assayed by ELISA; the expression changes of OPN mRNA in bone marrow of the CNSL patients were detected by RT-PCR. The results indicated that the serum OPN level was significantly higher in CNSL group (25.21 ± 6.87 ng/ml) than that in acute leukemia group (13.24 ± 2.73 ng/ml) (P < 0.001) and nontumorous group (3.14 ± 1.60 ng/ml) (P < 0.001); the serum OPN level (4.35 ± 1.50 ng/ml) in CNSL group with CR decreased obviously (P < 0.001) after therapy; RT-PCR analysis showed that the expression of OPN mRNA was higher in CNSL group as compared with other two groups (P < 0.01). It is concluded that the OPN expression may play a role in central nervous system infiltration of leukemia, the mechanism of which remains to need further clinical exploration.
Bone Marrow Examination ; Case-Control Studies ; Central Nervous System Neoplasms ; blood ; pathology ; Child, Preschool ; Female ; Humans ; Leukemia ; blood ; pathology ; Male ; Osteopontin ; blood ; metabolism

BACKGROUNDClinical outcome in patients with primary central nervous lymphoma (PCNSL) is variable and poorly predictable. This study investigated the association of clinical features and immune markers with prognosis of patients with PCNSL.

METHODSOne hundred and fifteen newly diagnosed PCNSL patients at the study institution were considered eligible for this study. Clinical characteristics and biochemical assay data were collected. Immunohistochemical staining of Cyclin D3, Cyclin E, Foxp1, and LMO2 were performed. All cases were followed-up regularly.

RESULTSThe common sites of involvement were frontal lobe (54.8%) and thalamus (16.5%). Diffuse large B-cell lymphoma composed of 96.5% of the cases. The median overall survival was 22 (4 - 41) months, and the 5-year survival rate was 22.8%. Age > 65 years, serum globulin > 40 g/L, large size of tumor, lymphocyte count ≥ 1 × 10(9)/L, and expression of Cyclin D3 and Cyclin E were associated with poor prognosis of PCNSL. Expressions of Foxp1, LMO2, and CD44 were not related to the survival. Expression of Cyclin E, large tumor size, and high serum globulin were independent prognostic factors for PCNSL.

CONCLUSIONSPCNSL prognosis is relatively poor. Age, high tumor burden, higher lymphocyte count, expression of Cyclin D3, and Cyclin E are inferior prognostic factors for PCNSL.

Adaptor Proteins, Signal Transducing ; metabolism ; Adult ; Aged ; Central Nervous System Neoplasms ; metabolism ; pathology ; Cyclin D3 ; metabolism ; Cyclin E ; metabolism ; Female ; Forkhead Transcription Factors ; metabolism ; Humans ; Immunohistochemistry ; LIM Domain Proteins ; metabolism ; Lymphoma ; metabolism ; pathology ; Male ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins ; metabolism ; Repressor Proteins ; metabolism ; Retrospective Studies ; Young Adult

OBJECTIVETo analyze the subtypes of primary diffuse large B cell lymphoma of the central nervous system (CNS DLBCL) and to explore the relationship between the subtype classification and prognosis.

METHODSImmunohistochemical staining was used to determine the expression of CD20, CD3, CD10, Bcl-6, Mum-1, CD5, Bcl-2, Ki-67, FOXP-1, GCET-1, BLIMP-1 and LMO-2 antigens on paraffin-embedded sections of 47 cases. Hans, Choi and Tally subtypes were classified, and univariate and multivariate analyses were used to elucidate the relationship between the subtypes and prognosis.

RESULTSIn the 47 cases, the expression of Bcl-2 in the tumor cells was 46.8%, CD10 4.3%, Bcl-6 70.2%, Mum-1 53.2%, GCET-1 36.2%, BLIMP-1 4.3%, FOXP-1 63.8% and LMO-2 19.2%. The positive rate of Ki-67 was 30% to 95%, with a median of 80%, of which 12 cases (25.5%) was > or = 90%. The Hans subtype classification showed 16 cases (34.0%) were of GCB type and 31 cases (66.0%) of non-GCB type. The Choi subtype classification showed 16 cases (34.0%) were of GCB type and 31 cases (66.0%) of ABC type. The Tally subtype classification showed 6 cases (12.8%) were of GCB type and 41 cases (87.2%) of non-GCB type.

CONCLUSIONSThe results of this study show that there is no significant correlation between the three subtypes and prognosis. The prognosis is correated with post-operative radiotherapy, chemotherapy and MTX therapy.

Adaptor Proteins, Signal Transducing ; metabolism ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Central Nervous System Neoplasms ; classification ; metabolism ; pathology ; therapy ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Forkhead Transcription Factors ; metabolism ; Humans ; Immunophenotyping ; methods ; Interferon Regulatory Factors ; metabolism ; Ki-67 Antigen ; metabolism ; LIM Domain Proteins ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; classification ; metabolism ; pathology ; therapy ; Male ; Methotrexate ; therapeutic use ; Middle Aged ; Neoplasm Proteins ; metabolism ; Neprilysin ; metabolism ; Positive Regulatory Domain I-Binding Factor 1 ; Prednisone ; therapeutic use ; Prognosis ; Proto-Oncogene Proteins ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Proto-Oncogene Proteins c-bcl-6 ; metabolism ; Repressor Proteins ; metabolism ; Retrospective Studies ; Serpins ; metabolism ; Survival Rate ; Vincristine ; therapeutic use ; Young Adult

OBJECTIVETo evaluate the value of FOXP1 and Cyclin E gene in primary central nervous system lymphoma(PCNSL) of immunocompetent patients on prognostic significance.

METHODSClinical data of 71 patients with newly diagnosed PCNSL from 2002 to 2007 was analyzed retrospectively. Immunohistochemistry method (HRP-EnVision(TM)) was performed to observe the expression of FOXP1 and Cyclin E gene in tumor tissue samples. The survival was analyzed by Kaplan-Meier survival curve, survival factors analysis by the Log-rank test and COX proportional hazards regression model.

RESULTSFOXP1 positive was observed in 35 of 51 patients (68.63%) and Cyclin E staining was present in 29 of 50 cases (58.00%). FOXP1(+) patients had a shorter overall survival (OS) than FOXP1(-) ones. 2-year OS rate in FOXP1(+) and FOXP1(-) patients were 23.33% and 73.56%, respectively(P = 0.0015). Cyclin E(+) patients had a shorter overall survival(OS) than cyclinE(-) ones. 2-year OS rate in Cyclin E(+) and Cyclin E(-) patients were 17.56% and 69.76%, respectively (P = 0.0017). Multivariate analysis showed that Cyclin E expression was an independent prognostic factor for shorter OS (P = 0.048). FOXP1 expression might be an important prognostic factor for shorter OS (P = 0.065).

CONCLUSIONCyclin E expression is an independent prognostic factor and FOXP1 expression is a possible prognostic factor for poor clinical outcome in patients with PCNSL.

Aged ; Aged, 80 and over ; Central Nervous System Neoplasms ; genetics ; metabolism ; Cyclin E ; genetics ; metabolism ; Female ; Forkhead Transcription Factors ; genetics ; metabolism ; Humans ; Lymphoma, Non-Hodgkin ; genetics ; metabolism ; Male ; Middle Aged ; Prognosis ; Repressor Proteins ; genetics ; metabolism ; Retrospective Studies ; Survival Rate