OBJECTIVETo investigate the expression of HER2/neu, Ki-67 and TK1 protein in meningiomas in correlation with tumor grades and recurrence.

METHODSTwenty cases of each of the following types of meningiomas were selected for the study, namely: the benign non-recurrent, recurrent benign, atypical and malignant, according to the World Health Organization (WHO) histological classification of nervous system, 2007. Immunohistochemistry study for HER2/neu, Ki-67 and TK1 protein was performed. HER2/neu gene amplification was detected using FISH. Cases with HER2 protein overexpression were studied by immunohistochemistry staining. The results of the biomarker assays were also used to study the correlationship with the tumor grades and tumor recurrency.

RESULTSImmunohistochemistry showed that the positive rates of HER2 expression in non-recurrence benign group, recurrence benign group, atypical group and malignant group were 3 cases (15%), 6 cases (30%), 7 cases (35%), and 10 cases (50%), respectively (P < 0.05). A higher tumor grade was correlated with a higher rate of HER2/neu expression. The Ki-67 and TK1 labeling index (LI) in non-recurrence group were lower than those in the atypical or malignant group (P < 0.05), whereas the atypical group had lower LI than that of the malignant group (P < 0.05). Higher levels of LI of Ki-67 and TK1 were correlated with higher tumor grades and recurrence of the benign meningiomas (P < 0.05). Expression of HER2 was positively correlated with Ki-67 and TK1 (r = 0.445, P < 0.01; r = 0.501, P < 0.01, respectively), and there was a positive correlation between Ki-67 and TK1 (r = 0.450, P < 0.01) as well. HER2/neu gene copy amplification in 7 of 26 cases (26.9%) of HER2 immunopositive meningiomas. The rates of HER2/neu gene amplification were 0 in tumors with 1+ immunopositivity, 4/6 in tumor with 2+ immunopositivity and 3/4 in tumor with 3+ immunopositivity. HER2/neu gene amplification in 3+ and 2+ immunopositive cases had no statistical significance (P > 0.05). Aneuploidy of chromosome 17 existed in 9 of 26 of HER2 immunopositive meningiomas (34.6%). However, the rates of chromosome 17 aneuploidy had no significant difference among tumors with variable HER2/neu imumopositivity (P > 0.05).

CONCLUSIONSHigh levels of HER2 and Ki-67 or TK1 expression correlate with the increase of tumor grades and tumor recurrence. HER2/neu gene amplification is seen in a subset of meningiomas with the protein expression (26.9%). A combination of biomarker study including HER2/neu, Ki-67 and TK1 may be useful in predicting the biological behavior of meningiomas.

Aneuploidy ; Chromosomes, Human, Pair 17 ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen ; metabolism ; Male ; Meningeal Neoplasms ; genetics ; metabolism ; pathology ; Meningioma ; genetics ; metabolism ; pathology ; Middle Aged ; Neoplasm Recurrence, Local ; Receptor, ErbB-2 ; genetics ; metabolism ; Thymidine Kinase ; metabolism

Alteration of apoptosis is related with progression and recurrence of atypical meningiomas (AMs). However, no comprehensive study has been conducted regarding histone modification regulating apoptosis in AMs. This study aimed to determine the prognostic values of certain apoptosis-associated factors, and examine the role of histone modification on apoptosis in AMs. The medical records of 67 patients with AMs, as diagnosed during recent 13 yr, were reviewed retrospectively. Immunohistochemical staining was performed on archived paraffin-embedded tissues for pro-apoptotic factors (CASP3, IGFBP, TRAIL-R1, BAX, and XAF1), anti-apoptotic factors (survivin, ERK, RAF1, MDM2, and BCL2), and the histone modifying enzymes (MLL2, RIZ, EZH1, NSD2, KDM5c, JMJD2a, UTX, and JMJD5). Twenty-six (38.8%) patients recurred during the follow-up period (mean duration 47.7 months). In terms of time-to-recurrence (TTR), overexpression of CASP3, TRAIL-R1, and BAX had a longer TTR than low expression, and overexpression of survivin, MDM2, and BCL2 had a shorter TTR than low expression (P<0.05). Additionally, overexpression of MLL2, UTX, and JMJ5 had shorter TTRs than low expression, and overexpression of KDM5c had a longer TTR than low expression. However, in the multi-variate analysis of predicting factors for recurrence, low expression of CASP3 (P<0.001), and BAX (P<0.001), and overexpression of survivin (P=0.007), and MDM2 (P=0.037) were associated with recurrence independently, but any enzymes modifying histone were not associated with recurrence. Conclusively, this study suggests certain apoptosis-associated factors should be associated with recurrence of AMs, which may be regulated epigenetically by histone modifying enzymes.
Adult ; Aged ; Aged, 80 and over ; Apoptosis/*genetics ; Apoptosis Regulatory Proteins/genetics ; Epigenesis, Genetic/genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Histone Code/genetics ; Histone Demethylases/*genetics ; Histone-Lysine N-Methyltransferase/*genetics ; Humans ; Longitudinal Studies ; Male ; Meningeal Neoplasms/*genetics/pathology ; Meningioma/*genetics/pathology ; Middle Aged ; Neoplasm Recurrence, Local/*genetics

Mantle cell lymphoma (MCL) is an uncommon type of gastrointestinal lymphoma. MCL is a distinct subtype of B-cell non-Hodgkin lymphomas. The major subtype of MCL is characterized by the presence of multiple lymphomatous polyposis (MLP), in which multiple polyps are observed along the gastrointestinal tract. The malignant cells express pan B-cell marker and the T-cell marker cluster of differentiation 5. The chromosomal translocation t(11;14)(q13;q32) that causes cyclin D1 overexpression is commonly observed on the cytogenetic analysis of MCL. Survival improvement has recently been achieved for patient with MCL by the successful introduction of monoclonal antibodies and dose-intensified approaches for treatment, including autologous stem cell transplantation strategies. Some reports suggest that there is an increased incidence of second malignancies in patients with MCL or lymphoma. We report a case of MCL involving the colon; the patient was a 60-year-old man who complained of low abdominal discomfort during defecation. During the workup, a meningioma was unexpectedly discovered. On analysis, the tumor was found to be a t(11;14)-negative and non-MLP-type MCL.
Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 14 ; Cyclin D1/metabolism ; Humans ; Lymphoma, Mantle-Cell/*diagnosis/genetics/metabolism ; Magnetic Resonance Imaging ; Male ; Meningeal Neoplasms/complications/*diagnosis/pathology ; Meningioma/complications/*diagnosis/pathology ; Middle Aged ; Positron-Emission Tomography ; Translocation, Genetic

Antigens, CD34 ; metabolism ; Carcinoma, Renal Cell ; metabolism ; pathology ; Central Nervous System Neoplasms ; metabolism ; pathology ; surgery ; ultrastructure ; Diagnosis, Differential ; Ependymoma ; metabolism ; pathology ; Hemangioblastoma ; metabolism ; pathology ; surgery ; ultrastructure ; Humans ; Meningeal Neoplasms ; metabolism ; pathology ; Meningioma ; metabolism ; pathology ; Mutation ; Neoplasm Recurrence, Local ; Prognosis ; Receptor, Epidermal Growth Factor ; metabolism ; Vimentin ; metabolism ; von Hippel-Lindau Disease ; genetics ; metabolism ; pathology ; surgery

Multiple endocrine neoplasia type 1 (MEN1) syndrome includes varying combinations of endocrine and non-endocrine tumors. There are also a considerable number of atypical MEN1 syndrome. In this case, a 68-yr-old woman was referred to the Department of Endocrinology for hypercalcemia. Five years ago, she had diagnosed as primary hyperaldosteronism and now newly diagnosed as parathyroid hyperplasia with laboratory and pathologic findings. Hurthle-cell thyroid cancer was also resected during the parathyroid exploration and small meningioma was found on brain MRI. Her general condition has markedly improved and her adrenal mass and meningioma are being closely observed now. We could find the loss of heterozygosity of the MEN1 locus in parathyroid glands, suggesting a MEN1-related tumor, but not a germline mutation. Considering a variety of phenotypic expression and a limitation of current molecular analysis, periodic follow up will be needed in patients with a MEN1-like phenotype.
Aged ; Base Sequence ; Brain/radionuclide imaging ; Female ; Humans ; Hyperaldosteronism/complications/*diagnosis ; Hyperparathyroidism, Primary/*diagnosis/etiology/pathology ; Loss of Heterozygosity ; Magnetic Resonance Imaging ; Meningeal Neoplasms/complications/*diagnosis/radionuclide imaging ; Meningioma/complications/*diagnosis/radionuclide imaging ; Mutation ; Parathyroid Glands/pathology ; Proto-Oncogene Proteins/genetics/metabolism ; Sequence Analysis, DNA ; Thyroid Neoplasms/complications/*diagnosis/pathology ; Tomography, X-Ray Computed