OBJECTIVETo characterize the cytogenetic alterations of esthesioneuroblastoma (ENB).

METHODSComparative genomic hybridization (CGH) was performed on genomic DNA extracted from 12 patients with primary ENB, 4 patients with tumor recurrence and 7 with metastasis. Equal amounts of biotin-labeled tumor DNA and digoxigenin-labeled normal reference DNA were hybridized to normal meta phase chromosomes. Tumor DNA was visualized by fluorescein (FITC) and normal DNA by rhodamin (TRITC ) and detected by fluorescence microscopy. The signal intensities of the different fluorochromes were quantitated as gray levels along the single chromosomes. The over-and under-represented DNA segments were determined by computation of FITC/TRITC ratio images and average ratio profiles.

RESULTSConsensus deletion regions were most frequently observed on chromosomes 1p, 2q, 3p/q, 4p/q, 5p/q, 6q, 8p/q, 9p, 10p/q, 11p, 12q, 13q, 18q, and 21q. DNA over-representations were identified on chromosomes 1p, 7q, 9q, 11q, 14q, 16p/q, 17p/q, 19p/q, 20p/q and 22p/q. The genetic pattern of ENB was distinct from that of other small round-cell tumor types and neuroblastomas. The deletion on chromosome band 1p21-p31 was associated with bad prognosis. In particular, all patients died whose tumors had combined 1p21-p31 deletion, with tumors in clinical stage C or D, and of low differentiation (grade III or IV). Clonality analysis revealed a high concordance between pairs of primaries and metastases.

CONCLUSIONCGH analysis identifies characteristic cytogenetic aberrations of esthesioneuroblastoma associated with its malignant phenotype.

Adolescent ; Adult ; Aged ; Bone Marrow Neoplasms ; genetics ; secondary ; Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 1 ; DNA, Neoplasm ; genetics ; Esthesioneuroblastoma, Olfactory ; genetics ; secondary ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Male ; Middle Aged ; Nasal Cavity ; Nose Neoplasms ; genetics ; pathology ; Prognosis

OBJECTIVETo observe the effect of Tiam-l gene silencing on the metastasis of human colorectal carcinoma cell line SW480 in nude mice by real-time whole-body fluorescence imaging.

METHODSEnhanced green fluorescence protein (EGFP)-labeled human colorectal carcinoma cells, SW480/EGFP(+)/Tiam-1(-) and SW480/EGFP(+), were implanted into nude mice via tail vein injection or orthotopic colonal inoculation, and real-time whole-body fluorescence imaging was performed to compare the difference in tumor progression and metastasis between the two cells.

RESULTSBoth SW480/EGFP(+) and SW480/ EGFP(+)/Tiam-1(-) cells stably expressed EGFP, and Tiam1 gene expression was reduced in SW480/EGFP(+)Tiam-1(-) to 30% of the expression level in SW480/EGFP(+) cells. The growth rate of the two cell lines had no significant difference in vitro (P>0.05), but SW480/EGFP(+)/Tiam1(-) cell proliferation and metastasis were depressed obviously in comparison with SW480/EGFP(+) in vivo (P<0.05).

CONCLUSIONTiam-1 gene may play an important role in invasion and metastasis of human colorectal cancer.

Animals ; Blotting, Western ; Bone Neoplasms ; genetics ; metabolism ; secondary ; Cell Line, Tumor ; Cell Survival ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; Diagnostic Imaging ; methods ; Female ; Fluorescence ; Gene Silencing ; Green Fluorescent Proteins ; chemistry ; genetics ; metabolism ; Guanine Nucleotide Exchange Factors ; genetics ; metabolism ; Immunohistochemistry ; Liver Neoplasms ; genetics ; metabolism ; secondary ; Lung Neoplasms ; genetics ; metabolism ; secondary ; Mice ; Mice, Nude ; Microscopy, Fluorescence ; Neoplasm Transplantation ; T-Lymphoma Invasion and Metastasis-inducing Protein 1 ; Transplantation, Heterologous

Adenocarcinoma, Follicular ; radiotherapy ; secondary ; Adolescent ; Adult ; Aged ; Bone Neoplasms ; secondary ; Carcinoma, Papillary ; radiotherapy ; secondary ; Child ; Chromosome Aberrations ; radiation effects ; Dose-Response Relationship, Radiation ; Humans ; Hypoparathyroidism ; etiology ; Iodine Radioisotopes ; administration & dosage ; Lung ; physiopathology ; Lung Neoplasms ; secondary ; Lymphatic Metastasis ; Middle Aged ; Parathyroid Glands ; physiopathology ; Salivary Glands ; physiopathology ; Thyroid Neoplasms ; genetics ; pathology ; radiotherapy

The formation of osteolytic bone lesions is a key process for osteolytic cancer to metastasize to the bone and is under the control of a set of transcription factors. Recently, the inhibitor of differentiation 1 (Id1) has been linked with angiogenesis, tumorigenesis, metastasis and bone formation. However, the function of Id1 during the process of bone destruction caused by cancer in vivo has not yet been elucidated. We, therefore, examined whether and how Id1 affects the ability of cancer to form osteolytic lesion in vivo. The study used a lentiviral vector overexpressing short hairpin RNA (shRNA) targeting Id1 gene. PC3 cells, a prostate cancer cell line, were transduced with Id1 shRNA or negative control (NC) shRNA before implantation in BALB/c mice. Cells were implanted in a tibial injection model. Tumor formation in bone was monitored by X-ray. The relationship between parathyroid hormone-related protein (PTHrP), an osteolytic factor, and Id1 was analyzed by using immunohistochemistry in tissue sections from osteolytic lesion of the BALB/c mice. Our results showed that Id1 shRNA delivery to PC3 cells by lentivirus caused efficient and stable Id1 gene silencing. In the intratibial model, PC3 cells produced primarily osteolytic lesions in the bone. Eleven of 14 mice in Id1 shRNA group but only 4 of 14 mice in the NC shRNA group developed osteolytic lesions with cortical destruction at 4th week. Mice treated with Id1 shRNA had larger tumor volume in the bone and larger cortical destruction. The expression of PTHrP protein in PC3 cells was not affected by Id1 knockdown in vivo. These results indicate that Id1 may down-regulate the ability of PC3 cells to form osteolytic lesions in vivo and the signal pathway needs to be further investigated.
Animals ; Bone Neoplasms ; genetics ; metabolism ; secondary ; Cell Line, Tumor ; Gene Silencing ; Humans ; Inhibitor of Differentiation Protein 1 ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Osteolysis ; genetics ; metabolism ; pathology ; Prostatic Neoplasms ; genetics ; metabolism ; pathology

PURPOSE: Bone is the most frequent site of metastasis among breast cancer patients. We investigated prognostic factors affecting survival following bone-only metastasis in breast cancer patients. MATERIALS AND METHODS: The medical records of breast cancer patients who were treated and followed at Gangnam Severance Hospital retrospectively reviewed to identify patients with bone-only metastasis. RESULTS: The median time from the diagnosis of bone-only metastasis to the last follow-up or death was 55.2 [95% confidence interval (CI), 38.6-71.9] months. The Kaplan-Meier overall survival estimate at 10 years for all patients was 34.9%. In the multivariate Cox regression model, bisphosphonate treatment [hazard ratio=0.18; 95% CI, 0.07-0.43], estrogen receptor positivity (hazard ratio=0.51; 95% CI, 0.28-0.94), and solitary bone metastasis (hazard ratio=0.32; 95% CI, 0.14-0.72) were significantly associated with longer overall survival in the bone-only recurrence group. Among the treatment modalities, only bisphosphonate treatment was identified as a significant prognostic factor. CONCLUSION: Identifying the factors influencing breast cancer mortality after bone-only metastasis will help clarify the clinical course and improve the treatment outcome for patients with breast cancer and bone-only metastasis. Bisphosphonates, as a significant prognostic factor, warrant further investigation.
Adult ; Antineoplastic Agents/therapeutic use ; Bone Neoplasms/drug therapy/genetics/*secondary ; Breast Neoplasms/drug therapy/genetics/*pathology ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Prognosis ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Regression Analysis ; Retrospective Studies ; Survival Analysis

OBJECTIVETo study the clinicopathologic features of malignant phyllodes tumors (PT) by histopathologic analyses, immunohistochemical profiling and DNA content assay, and evaluation of the clinical outcome.

METHODSTen patients with malignant PT from 1999 to 2013 who were treated by surgery were enrolled in this study. The morphologic characteristics were studied under light microscope, standard two-step EnVision method of immunohistochemical staining was used to assess the expression of CK5/6, CKpan, 34β E12, desmin, p63, ER-α, PR, Ki-67, CD34, SMA, p53, p16, bcl-2 and CD117 in the tumors. The corresponding paraffin blocks were also used for flow cytometric DNA content assay. These data were correlated with the follow-up results.

RESULTSThe median age of onset was 46.5 years old. The mean tumor size was 7.4 cm (2.0-25.0 cm). At the end of the follow-up period (22 to 125 months), there were tumor recurrences in 3/8 patients and the median time of recurrence was 24 months. Metastasis occurred in 3/8 patients who all died of the tumors. PT had heterogeneous histology, with stromal overgrowth with leaf-like projections, periductal stromal overgrowth, and most commonly, diffuse stromal overgrowth with sarcomatous differentiation. The mean positive index of Ki-67 was 11.4%. The stromal tumor cells were positive for CD34, SMA, p53, p16, and bcl-2 in 3/10, 9/10, 6/10, 8/10, and 4/10 cases, respectively. CD117,ER-α and PR were negative. Interpretable DNA histograms were obtained in nine cases with triploidy in two cases.

CONCLUSIONSThe diagnosis of malignant PT should be considered based on the diversity of growth patterns and heterogeneous histology.Ki-67 and CD34 are valuable diagnostic and prognostic factors in patients with malignant PT. Tumors with diffuse stromal overgrowth, heterologous elements, Ki-67 ≥ 20% or aneuploidy are more likely to metastasize.

Adult ; Aged ; Antigens, CD34 ; metabolism ; Bone Neoplasms ; secondary ; Breast Neoplasms ; genetics ; metabolism ; pathology ; surgery ; therapy ; Chemoradiotherapy, Adjuvant ; Diploidy ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Lung Neoplasms ; secondary ; Mastectomy ; methods ; Middle Aged ; Neoplasm Recurrence, Local ; Phyllodes Tumor ; genetics ; metabolism ; pathology ; secondary ; surgery ; therapy ; Triploidy

The purpose of this study was to examine the association of the expression of Sox4 and β-catenin with the prognosis of osteosarcoma. A total of 108 cases of conventional osteosarcoma were involved in this study and 28 cases of osteochondroma served as controls. The expression of Sox4 and β-catenin was detected by using immunohistochemical staining and Western blotting. The results showed that Sox4 and β-catenin were over-expressed in 67 (62.03%) and 62 (57.41%) of 108 osteosarcoma cases, while in only 3 (10.71%) and 5 (17.86%) of 28 controls, respectively (P<0.05 for all). The expression of Sox4 and β-catenin was associated with the distant metastasis, pathological grade and Enneking stage of patients with osteosarcoma (P<0.05 for all). The mean overall survival time and the 5-year-survival rate in osteosarcoma patients with Sox4 and β-catenin over-expressed were significantly reduced as compared with those in Sox4 and β-catenin low-expression group (P<0.05 for all). Cox multifactor regression analysis revealed that the distant metastasis, Enneking stage, and the expression of Sox4 and β-catenin were independent risk factors of patients with osteosarcoma (P<0.05 for all). The findings indicated that overexpression of Sox4 and β-catenin is associated with a poor prognosis of osteosarcoma.
Adolescent ; Adult ; Biomarkers, Tumor ; genetics ; metabolism ; Bone Neoplasms ; metabolism ; pathology ; Case-Control Studies ; Child ; Female ; Humans ; Lung Neoplasms ; metabolism ; secondary ; Male ; Middle Aged ; Osteosarcoma ; metabolism ; pathology ; SOXC Transcription Factors ; genetics ; metabolism ; beta Catenin ; genetics ; metabolism

OBJECTIVETo study the cytogenetic mechanism of bone metastasis of human prostate cancer (PCa).

METHODSWe analyzed chromosome variation by comparative genomic hybridization in 18 patients with prostate cancer to determine the chromosome variants associated with bone metastasis, and focused on 7 microsatellite sites on chromosome 10 for the detection of the loss of heterozygosity (LOH) by PCR-based microsatellite polymorphism analysis.

RESULTSIn the 11 samples with bone metastasis, the variation rate of chromosome 10 was 90.9% (10/11), significantly higher than that of the others (P < 0.01). A much higher LOH frequency was observed at the 7 microsatellite loci on chromosome 10 and the highest located in 10q24. 2-q25.3 (D10S1693-D10S587) in the PCa patients with bone metastasis.

CONCLUSIONThere is a high-frequency LOH region in 10q24. 2-q25.3 (D10S1693-D10S587) on chromosome 10 in PCa patients with bone metastasis, which may be potentially involved in PCa progression and specific bone metastasis.

Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms ; genetics ; secondary ; Chromosomes, Human, Pair 10 ; Comparative Genomic Hybridization ; Humans ; Loss of Heterozygosity ; Male ; Middle Aged ; Neoplasm Metastasis ; genetics ; Prostatic Neoplasms ; genetics ; pathology

Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients. The skeleton is frequently targeted by disseminated cancer cells and represents the sole site of spread in more than 80% of prostate cancer cases. Compatibility between select malignant phenotypes and the microenvironment of colonized tissues is broadly recognized as the culprit for the organ-tropism of cancer cells. Here, we review our recent studies showing that the expression of platelet-derived growth factor receptor alpha (PDGFRα) supports the survival and growth of prostate cancer cells in the skeleton and that the soluble fraction of bone marrow activates PDGFRα in a ligand-independent fashion. Finally, we offer pre-clinical evidence that this receptor is a viable target for therapy.
Animals ; Antibodies, Monoclonal ; therapeutic use ; Bone Marrow ; enzymology ; pathology ; Bone Neoplasms ; prevention & control ; secondary ; Enzyme Activation ; Humans ; Male ; Prostatic Neoplasms ; drug therapy ; enzymology ; pathology ; Receptor, Platelet-Derived Growth Factor alpha ; antagonists & inhibitors ; genetics ; immunology ; metabolism ; Signal Transduction ; Transcriptional Activation

OBJECTIVETo investigate the expression of p21(WAF1) gene in human osteosarcoma and their relationships with clinicopathological parameters and prognostic value.

METHODSThe p21(WAF1) gene mRNA and p21 protein expression in 45 osteosarcoma and 10 fibrous dysplasia of bone specimens were analyzed by in situ hybridization and immunohistochemistry respectively.

RESULTS(1) The positive rate of p21 protein expression in osteosarcoma was 17.7% (8/45). (2) The expression rate in high proliferation (4/10) significantly higher than that in low proliferation (4/35) osteosarcoma (chi2 = 4.34, P < 0.05). (3) The positive rate of p21(WAF1) mRNA expression in osteosarcoma was 42.2% (19/45). The expression rate in high proliferation (6/10) significantly higher than that in low proliferation (13/35) osteosarcoma (chi2 = 20.6, P < 0.01). (4) The survival time after operation of the patients with p21(WAF1) mRNA expression were higher than that of the patients with p21(WAF1) mRNA negative expression (P < 0.05).

CONCLUSIONS(1) With the increase in degree of malignancy, the expression of p21(WAF1) mRNA and p21 protein in osteosarcoma tend decrease. (2) The expression of p21(WAF1) mRNA has a definite value in judging prognosis in osteosarcoma.

Adolescent ; Adult ; Bone Neoplasms ; metabolism ; pathology ; Cyclin-Dependent Kinase Inhibitor p21 ; biosynthesis ; genetics ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms ; metabolism ; secondary ; Male ; Neoplasm Staging ; Osteosarcoma ; metabolism ; pathology ; Prognosis ; RNA, Messenger ; biosynthesis ; genetics ; Survival Rate