BACKGROUND: DNA hypermethylation is a common epigenetic finding in human cancers and is closely associated with transcriptional silencing. In the present study, we investigated the proportion of colorectal neoplasms that showed the adenoma-carcinoma progression and vimentin gene methylation. METHODS: Methylation status of the vimentin gene was examined in nontumoral mucosa, adenomas, and adenocarcinomas from 45 colorectal cancer patients who had adenoma and adenocarcinoma together. Methylation status was determined by bisulfite modification and the methylation-specific polymerase chain reaction. The expression of the vimentin gene product was also examined by immunohistochemistry. RESULTS: Promoter methylation of vimentin was detected in 80% (36 out of 45 cases) of adenocarcinomas, 82.2% (37 of 45) of adenomas, and 28.9% (13 of 45) of normal epithelia, and the difference between neoplastic and normal specimens was statistically significant (p < 0.001). However, no significant correlations were observed between methylation frequency and clinicopathologic variables. Immunohistochemically, vimentin expression was not observed in either normal epithelial cells or tumor cells. Protein expression and vimentin promoter methylation were not associated. CONCLUSIONS: The frequency of aberrant methylation of the vimentin gene was high in colonic adenomas and adenocarcinomas. This result suggests that the methylation status of vimentin may be clinically beneficial in screening for colorectal cancer patients and may be helpful in clarifying colorectal cancer biology.
Adenocarcinoma ; Adenoma ; Biology ; Colon ; Colorectal Neoplasms ; DNA ; Epigenomics ; Epithelial Cells ; Humans ; Mass Screening ; Methylation ; Mucous Membrane ; Polymerase Chain Reaction ; Sulfites ; Vimentin

BACKGROUND: This study was designed to examine the prevalence of aberrant promoter methylation in a selected panel of genes potentially involved in lymphoid tumors. METHODS: The promoter hypermethylation status of MGMT, DAPK1, hMLH1, CDH1, SHP1, and HIC1 was measured by methylation-specific PCR for 82 cases of B-cell lymphoma. Immunohistochemical staining using MGMT and SHP1 antibodies was conducted on 43 out of 82 cases. RESULTS: The number of MGMT aberrant methylations was lower in diffuse large B-cell lymphoma (DLBCL) than in other malignant lymphomas. The methylation of DAPK1 was frequently detected in follicular lymphoma (FL), marginal zone B-cell lymphoma (MZL) and DLBCL. With one exception, methylation of hMLH1 was not observed in B-cell lymphomas. The methylation frequency of CDH1, and HIC1 was similar in B-cell lymphomas. However, the methylation of SHP1 gene was more frequently observed in cases of FL, DLBCL, and MZL than in chronic lymphocytic lymphoma. MGMT and SHP1 promoter methylation were inversely correlated with the protein expression observed upon immunohistochemical staining. CONCLUSIONS: Aberrant promoter methylation of multiple genes occurs with variable frequency throughout the B-cell lymphomas, and methylation of hMLH1 is rarely observed in B-cell lymphomas.
Antibodies ; B-Lymphocytes ; DNA ; DNA Methylation ; Leukemia, Lymphocytic, Chronic, B-Cell ; Lymphoma ; Lymphoma, B-Cell ; Lymphoma, B-Cell, Marginal Zone ; Lymphoma, Follicular ; Methylation ; Polymerase Chain Reaction ; Prevalence

Malignant pleural effusion in multiple myeloma (MM) is extremely rare and is associated with poor prognosis. We experienced two cases of MM IgA type with malignant pleural effusion. The diagnoses were based on characteristic cytology and CD138 immunocytochemistry. The patients received several cycles of combination chemotherapy, since symptoms were more aggressive with an uncontrolled pleural effusion. We review the clinical features of these cases and literature concerning myelomatous pleural effusion.
Drug Therapy, Combination ; Humans ; Immunoglobulin A ; Immunohistochemistry ; Multiple Myeloma ; Pleural Effusion ; Pleural Effusion, Malignant ; Prognosis

BACKGROUND: HPV-other samples are designated as being positive on HPV-PCR, but negative when using specific HPV hybridization probes. We wanted to determine the types on the HPV-other samples by performing sequencing, and to know the pathologic status of the uterine cervix according to the HPV type detected on sequencing. METHODS: For HPV genotying, we used the commercially available HPV DNA Chip test, which contains 15 types of high-risk HPV and 9 types of low-risk HPV. The HPV DNA sequencing was performed for the HPV-other samples of 209 patients who subsequently underwent cervical biopsy. RESULTS: For 204 of the 209 samples, the HPV types detected by sequencing were absent types at used HPV DNA chip. For the remaining 5 samples, sequencing was impossible due to mixed peaks. HPV-81 (19.6%), HPV-61 (18.6%), HPV-62 (16.7%) and HPV-84 (13.9%) were frequently detected. For the HPV-81, -62, -71, and -72 samples, most of the samples displayed normal or LSIL. However, HPV-84 and -61 were more associated with HSIL or worse, as compared to the other types. Conclusion: HPV-81, -61, -62 and -84 were frequently found on sequencing analysis of the HPV-other samples. The pathologic status was diverse, according to the HPV type detected on sequencing.
Biopsy ; Cervix Uteri ; Chimera ; DNA ; Female ; Humans ; Oligonucleotide Array Sequence Analysis ; Papillomaviridae ; Sequence Analysis, DNA

Splenic metastasis from gynecologic tumors is extremely rare, especially in the absence of apparent disease at other sites. We report two patients that underwent splenectomy for a solitary splenic metastasis from uterine cervical carcinoma. In case 1, a 54-year-old woman with FIGO Stage IIb squamous cell carcinoma of the uterine cervix treated with radiotherapy and chemotherapy developed a solitary splenic metastasis 10 months after initial treatment. In case 2, a 46-year-old woman with FIGO Stage IIb adenocarcinoma of the uterine cervix treated with radiotherapy and chemotherapy was found to have a solitary splenic metastasis 11 months after treatment. Thus all abdominal organs including the spleen must be evaluated for metastases during follow-up of gynecologic tumors.
Female ; Humans ; Adenocarcinoma ; Neoplasm Metastasis

Aged ; Aged, 80 and over ; Esophagus ; pathology ; virology ; Herpes Simplex ; diagnosis ; genetics ; pathology ; Humans ; In Situ Hybridization ; Male ; Middle Aged ; Simplexvirus ; genetics

Claudin-7 has recently been suggested to be a distal nephron marker. We tested the possibility that expression of claudin-7 could be used as a marker of renal tumors originating from the distal nephron. We examined the immunohistochemical expression of claudin-7 and parvalbumin in 239 renal tumors, including 179 clear cell renal cell carcinoma (RCC)s, 29 papillary RCCs, 20 chromophobe RCCs, and 11 renal oncocytomas. In addition, the methylation specific-PCR (MSP) of claudin-7 was performed. Claudin-7 and parvalbumin immunostains were positive in 3.4%, 7.8% of clear cell RCCs, 34.5%, 31.0% of papillary RCCs, 95.0%, 80.0% of chromophobe RCCs, and 72.7%, 81.8% of renal oncocytomas, respectively. The sensitivity and specificity of claudin-7 in diagnosing chromophobe RCC among subtypes of RCC were 95.0% and 92.3%. Those of parvalbumin were 80.0% and 88.9%. The expression pattern of claudin-7 was mostly diffuse in chromophobe RCC and was either focal or diffuse in oncocytoma. All of the cases examined in the MSP revealed the presence of unmethylated promoter of claudin-7 without regard to claudin-7 immunoreactivity. Hypermethylation of the promoter might not be the underlying mechanism for loss of its expression in RCC. Claudin-7 can be used as a useful diagnostic marker in diagnosing chromophobe RCC and oncocytoma.
Tumor Markers, Biological/metabolism ; Tumor Cells, Cultured ; Tissue Distribution ; Sensitivity and Specificity ; Reproducibility of Results ; Nephrons/metabolism ; Neoplasm Proteins/metabolism ; Membrane Proteins/analysis/*metabolism ; Kidney Neoplasms/*diagnosis/*metabolism ; Humans ; Carcinoma, Renal Cell/*diagnosis/*metabolism ; Adenoma, Oxyphilic/*diagnosis/*metabolism

BACKGROUND: Elevated levels of microsatellite alterations at selected tetranucleotide repeat regions (EMAST) have been recently described, and they are a distinct type of microsatellite instability (MSI). We investigated the prevalence of EMAST in squamous cell carcinoma (SCC) of the uterine cervix and we determined the correlation between EMAST and the clinicopathologic parameters, HPV infection and the p53 mutation. METHODS: We examined the 3 mono-, 3 di-, and 5 tetranucleotide repeat markers in 47 cases of SCC, and we performed immunohistochemical staining for p53. HPV detection and genotyping was performed using a commercially available HPV DNA chip. RESULTS: Thirteen out of 47 cases (27.7%) were EMAST(+) with at least one of five tetranucleotide repeat markers. However, MSI at mono- and dinucleo- tide markers was noted in only one case (2.1%). EMAST was not related with stage, size, lymph node metastasis, vascular/lymphatic invasion or the depth of invasion. Positive immunostaining for p53 was significantly more common in EMAST(+) tumors than in the EMAST(-) tumors (p=0.04). HPV-infection was positive in 32 cases. EMAST was not correlated with the state of HPV infection state or the HPV genotype. CONCLUSIONS: 27.7% of the invasive SCCs of the uterine cervix exhibited EMAST, and EMAST in the SCC of the uterine cervix was significantly associated with the p53 mutation.
Carcinoma, Squamous Cell ; Cervix Uteri ; Female ; Genotype ; Lymph Nodes ; Microsatellite Instability* ; Microsatellite Repeats* ; Neoplasm Metastasis ; Oligonucleotide Array Sequence Analysis ; Prevalence

BACKGROUND: Angiogenesis, which is essential for tumor growth, is known to occur in the extravascular stroma. However, vascular structures were noted in intravascular tumor emboli in surgical specimens. This prompted our investigation of the frequency and morphology of angiogenesis in tumor emboli. METHODS: Hematoxylin-eosin stained specimens were reviewed for tumor emboli, in 21 cases of stomach adenocarcinoma and 22 cases of colon adenocarcinoma. The cases were examined with immunohistochemistry using antibodies against epithelial antigen (cytokeratin), endothelial antigens (CD31, CD34), lymphatic endothelial antigen (D2-40), and proliferation-associated antigen (MIB1). RESULTS: Endothelial cells were observed in 16 tumor emboli among four (19.1%) of the 21 cases of stomach adenocarcinoma and in 32 tumor emboli among four (18.2%) of the 22 cases of colon adenocarcinoma. The endothelial cells in the tumor emboli showed papillary ingrowth from the vessel wall, formation of vascular lumens, scattered distribution, or surface coating of the emboli. Some of the endothelial cells in the tumor emboli were D2-40-positive, and some were MIB1- positive. CONCLUSIONS: These findings demonstrated that angiogenesis occurs in intravascular tumor emboli as well as in the extravascular stroma. Angiogenesis in the tumor emboli may reflect an active process and may facilitate tumor growth.
Adenocarcinoma ; Antibodies ; Colon ; Endothelial Cells ; Immunohistochemistry ; Stomach

BACKGROUND: Giant cell tumors (GCT(s)) of bone are benign but can be locally aggressive neoplasms. Their clinical behavior has been difficult to predict on the basis of histology alone. This study investigated the neovascularization and expression of vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase-9 (MMP-9) in GCT(s) of bone; in addition we evaluated their relationship to clinical behavior. METHODS: We evaluated the microvessel number and density in 33 samples of giant cell tumor using CD34 immunohistochemistry. In addition, we examined the immunohistochemical expression of VEGF and MMP-9. RESULTS: The microvessel number alone, not the microvessel density, had statistical association with the clinical stage of GCT(s) (p=0.045). The proportion of cases with strong expression of VEGF increased with advancing clinical stage, however, these results were not statistically significant (p=0.257). The percentage of the cases with strong expression of MMP-9 also increased with advancing clinical stage and this was statistically significant (p=0.022). CONCLUSIONS: These results suggest that intratumor microvessel count and the expression of MMP-9 correlate with GCT stage. Evaluation of their expression may therefore provide prognostic information on the aggressive behavior of GCT(s) of bone.
Giant Cell Tumor of Bone ; Giant Cell Tumors* ; Giant Cells* ; Immunohistochemistry ; Matrix Metalloproteinase 9 ; Matrix Metalloproteinases ; Microvessels ; Prognosis ; Vascular Endothelial Growth Factor A*