BACKGROUND: The expression of the inhibitor of apoptosis proteins (IAPs) family has not been fully investigated in colorectal carcinomas. This study investigated IAP expression in colorectal carcinomas and assessed their prognostic significance. METHODS: Livin, XIAP, and SMAC/DIABLO expression was assessed by immunohistochemistry in 159 colorectal carcinomas. Correlations between protein expression and clinicopathological features were evaluated. The survival data analysis was estimated according to the Kaplan-Meier method. RESULTS: Increased expression of IAPs in cancer tissues compared to surrounding nonneoplastic counterparts was observed in 67 cases (42.1%) for Livin, 50 cases (31.4%) for XIAP, and 68 cases (42.8%) for SMAC. A significant correlation was found between Livin expression and tumor differentiation, and SMAC expression and tumor location. The recurrence-free and overall survival of patients with low Livin expression were inferior to those of patients with high Livin expression (p=0.054 and 0.095, respectively). High XIAP expression was significantly associated with shorter progression-free survival (p= 0.041). CONCLUSIONS: Our study demonstrated that altered expression of IAP family members, including Livin, XIAP, and SMAC, is frequent in colorectal carcinoma. This result suggests that high Livin expression and low XIAP expression may be a favorable prognostic implication related to patient survival.
Apoptosis ; Colorectal Neoplasms ; Disease-Free Survival ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; Intracellular Signaling Peptides and Proteins ; Mitochondrial Proteins ; Prognosis ; Proteins ; Statistics as Topic ; X-Linked Inhibitor of Apoptosis Protein

OBJECTIVE: Cardiomyopathy, a popular diagnosis that always obscures more than it reveals, nevertheless has several characteristic histological features. These prominently include widespread focal myocardial fibrosis and associated hypertrophy of surviving cardiac myocyte. In fact, focal noninflammatory degeneration (not necrosis) has been demonstrated as a feature of many forms of cardiac hypertrophy. We hypothesized that this loss of myocardial cells in dilated cardiomyopathy (DCMP) may result from cell death by apoptosis. METHODS: Endomyocardial biopsy specimens from the right ventricles of six patients who suffered from DCMP were studied, and myocardial specimens from two persons who died in motor vehicle accidents were used as negative controls. For identification of apoptosis, immunohistochemistry with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling was performed. In addition, apoptosis was confirmed morphologically by confocal laser scanning microscopy with propidium iodide. RESULTS: Apoptosis, that was represented by an apoptotic index ranging from 19.8 to 25.4+ACU-, could be extensively seen in myocytes and also rarely in non-myocytes of interstitium and vascular endothelium. Morphologically, there were a lot of nuclei with clumps of condensed chromatin, suggestive of apoptosis. CONCLUSION: The present study demonstrated that myocyte loss in DCMP might be mainly due to the apoptosis of myocytes and interstitial cells, rather than inflammation or cell necrosis.
Adult ; Analysis of Variance ; Apoptosis/physiology+ACo- ; Biopsy, Needle ; Cardiomyopathy, Congestive/physiopathology ; Cardiomyopathy, Congestive/pathology+ACo- ; Caspases/analysis ; Enzyme Precursors/analysis ; Female ; Human ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Microscopy, Confocal ; Middle Age ; Myocardium/pathology+ACo- ; Reference Values ; Statistics, Nonparametric

PURPOSE: Oncogene c-erbB2 produces a transmembrane protein similar in structure to the tyrosine kinase family. Overexpression of c-erbB2 is known to lower the survival rate of breast cancer patients. c-erbB2 protein is an important antigen for tumor specific cytotoxic T lymphocytes induction that is dependent on its presentation as stably complexed with HLA-A2. In 1997, Nistico P reported low frequency of c-erbB2 proto-oncogene overexpression in HLA A2 positive breast cancer patients. And then in this study, correlation of HLA-A2 and the c-erbB2 expression was investigated in breast cancer patients. MATERIALS AND METHODS: HLA-A DNA typing by locus-specific generic PCR and by hybridization with sequence-specific oligonucleotide probes (SSOP) was performed on peripheral blood lymphocytes from 52 breast cancer patients (a PCR-SSOP typing method, involving a PCR amplification in conjunction with digoxigenin labelled sequence-specific oligonucleotide probes). To determine c-erbB2 expression, immunohistochemistry from paraffin-embedded tissues in a series of 47 patients with available tissue blocks was performed by use of rabbit anti-human c-erbB2 oncoprotein (DAKO, Glostrup, Denmark). And then we statistically analyzed the relation between the expressions of HLA-A2 and c-erbB2 in breast cancer patients. RESULTS: 29 out of 52 patients (55.8%) were HLA-A2 positive. 23.4% (11out of 47 patients) of breast cancer patients overexpressed c-erbB2. The patients with c-erbB2 overexpression showed lower estrogen receptor positivity compared to those without c-erbB2 overexpression (10.5%, vs 33.3%). HLA-A2 positive patients showed 18.5% (5/27) of overexpression and HLA-A2 negative patients showed 30.0% (6/20) of c-erbB2 overexpression (p=0.283). CONCLUSIONS: We observed no correlation between HLA-A2 and prognostic factors in breast cancer such as tumor size, axillary nodal status. However, our results showed a tendency without statistical significance between HLA-A2 and high frequency of c-erbB2 overexpression. More accumulation of patients will be needed for better conclusions.
Breast Neoplasms* ; Breast* ; Digoxigenin ; DNA Fingerprinting ; Estrogens ; HLA-A Antigens ; HLA-A2 Antigen* ; Humans ; Immunohistochemistry ; Lymphocytes ; Oligonucleotide Probes ; Oncogenes ; Polymerase Chain Reaction ; Protein-Tyrosine Kinases ; Proto-Oncogenes ; Statistics as Topic ; Survival Rate ; T-Lymphocytes, Cytotoxic

OBJECTIVE: To validate contrast-enhanced power Doppler ultrasonography (PD US) for the evaluation of synovial vascularity in an arthritic rabbit knee model in correlation with MR and histological findings. MATERIALS AND METHODS: Power Doppler ultrasonography was performed for carrageenin-induced arthritic left knee and control right knee of 13 rabbits, first without and then with sonic contrast agent enhancement (Levovist, Schering, Berlin Germany), followed by gadolinium-enhanced MR imaging. Synovial vascularity was quantitatively assessed by calculating the color pixel area in power Doppler sonography using a computer-aided image analysis program and by grading the enhancement on MR images: grade 1, enhancement of knee joint is less than one-third of the area; grade 2, one-third to two-thirds enhancement; and grade 3, more than two-thirds enhancement. Microvessel density (MVD) was measured on slides stained immunohistochemically for CD31 antigen for histological assessment. RESULTS: The mean area of color pixels in PD US changed from 4.37 to 16.42 mm2 in the arthritic knee after enhancement (p < 0.05), whereas it changed from 0.77 to 2.31 mm2 in the control knee (p < 0.05). Arthritic knees had greater power Doppler signal than control knees both before and after contrast administration (p < 0.05). The average MVD was 88 in arthritic knees and 46 in control knees. MVDs correlated with color pixel areas of contrast-enhanced power Doppler imaging in arthritic knees. In MR grading of arthritic knees, five were grade 2 and eight were grade 3. MVD and PD US revealed no significant difference between grade 2 and 3 arthritic knees (p > 0.05). CONCLUSION: Sonic contrast-enhanced PD US improves the visualization of synovial vascularity and allows quantitative measurement in experimentally induced rabbit arthritic knees.
Animals ; Contrast Media ; Gadolinium DTPA/diagnostic use ; Image Processing, Computer-Assisted ; Immunohistochemistry ; Magnetic Resonance Imaging ; Osteoarthritis, Knee/pathology/*ultrasonography ; Polysaccharides/diagnostic use ; Rabbits ; Statistics, Nonparametric ; Synovial Membrane/*blood supply/pathology/ultrasonography ; *Ultrasonography, Doppler

OBJECTIVETo investigate the involvement of transient receptor potential vanilloid receptor 1 (TRPV1) in the facial inflammatory pain in relation to thermal hyperalgesia and cold pain sensation.

METHODSFacial inflammatory pain model was developed by subcutaneous injection of turpentine oil (TO) into rat facial area. Head withdrawal thermal latency (HWTL) and head withdrawal cold latency (HWCL) were measured once a day for 21 d after TO treatment using thermal and cold measurement apparatus. The immunohistochemical staining, cell-size frequency analysis and the survey of average optical density (OD) value were used to observe the changes of TRPV1 expression in the neurons of the trigeminal ganglion (TG), peripheral nerve fibers in the vibrissal pad, and central projection processes in the trigeminal sensory nuclei caudalis (Vc) on day 3, 5, 7, 14, and 21 after TO injection.

RESULTSHWTL and HWCL decreased significantly from day 1 to day 14 after TO injection with the lowest value on day 5 and day 3, respectively, and both recovered on day 21. The number of TRPV1-labeled neurons increased remarkably from day 1 to day 14 with a peak on day 7, and returned back to the normal level on day 21. In control rats, only small and medium-sized TG neurons were immunoreactive (IR) to TRPV1, and the TRPV1-IR terminals were abundant in both the vibrissal pad and the Vc. Within 2 weeks of inflammation, the expression of TRPV1 in small and medium-sized TG neurons increased obviously. Also the TRPV1 stained terminals and fibers appeared more frequent and denser in both the vibrissal pad skin and throughout laminae I and the outer zone of laminae II (IIo) of Vc.

CONCLUSIONFacial inflammatory pain could induce hyperalgesia to noxious heat and cold stimuli, and result in increase of the numbers of TRPV1 positive TG neurons and the peripheral and central terminals of TG. These results suggest that the phenotypic changes of TRPV1 expression in small and medium-sized TG neurons and terminals might play an important role in the development and maintenance of TO-induced inflammatory thermal hyperalgesia and cold pain sensation.

Animals ; Cold Temperature ; Facial Pain ; chemically induced ; metabolism ; physiopathology ; Hot Temperature ; Immunohistochemistry ; Male ; Neurons ; cytology ; metabolism ; Pain Threshold ; physiology ; Rats ; Rats, Sprague-Dawley ; Statistics, Nonparametric ; TRPV Cation Channels ; metabolism ; Thermosensing ; physiology ; Trigeminal Ganglion ; cytology ; metabolism ; Turpentine ; administration & dosage

OBJECTIVETo study the therapeutic effect of nimodipine on experimental brain injury.

METHODSExperimental and control rabbits were subjected to a closed head injury. In one group nimodipine was given intravenously and the effect evaluated by electron microscopy, brain water content, calcium levels, transcranial Doppler, and intracranial pressure monitoring.

RESULTSIn rabbits treated with nimodipine the level of neuronal cytosolic free calcium was markedly decreased. There were less cellular damage and less spasm of the middle cerebral artery seen on electron microscopy. No difference regarding intracranial pressure changes between the two groups was noted.

CONCLUSIONSNimodipine has a protective action on brain injury by blocking a series of pathological reactions induced by neuronal calcium overload, and by reducing the spasm of brain vessels and improving cerebral blood flow.

Animals ; Biopsy, Needle ; Brain Edema ; prevention & control ; Brain Injuries ; drug therapy ; pathology ; Calcium Channel Blockers ; pharmacology ; Disease Models, Animal ; Female ; Immunohistochemistry ; Infusions, Intravenous ; Male ; Nimodipine ; pharmacology ; Probability ; Rabbits ; Reference Values ; Sensitivity and Specificity ; Statistics, Nonparametric

BACKGROUND/AIMS: The usefulness of immunohistochemistry to screen for the microsatellite instability (MSI) phenotype in gastric cancer remains unclear. Moreover, the prognostic value of MSI phenotypes in gastric cancer has been debated. METHODS: The clinicopathologic parameters and survival outcomes of 203 MSI-high (MSI-H) and 261 microsatellite-stable (MSS) advanced gastric cancers (AGCs) were compared. Next, we compared the immunohistochemistry results for hMLH1 and hMSH2 with those of a polymerase chain reaction (PCR)-based method. Kaplan-Meier curves and a Cox proportional hazard regression model were used to conduct survival analyses. RESULTS: The MSI-H AGCs were correlated with older age (p<0.001), female gender (p=0.018), distal location (p<0.001), larger size (p=0.016), and intestinal type (p<0.001). Multivariate analysis revealed that the MSI-H phenotype was an independent favorable factor that was related to overall survival in patients with AGC (p<0.001). Compared with the PCR-based analysis, immunohistochemistry exhibited high sensitivity (91.1%) and specificity (98.5%) in the detection of MSI phenotypes. CONCLUSIONS: MSI-H gastric cancers have distinct clinicopathologic features and better prognoses, which suggests the necessity of MSI analysis in gastric cancer. Immunohistochemistry can be a useful and reliable screening method in the assessment of MSI status in gastric cancer.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Immunohistochemistry/*statistics & numerical data ; Kaplan-Meier Estimate ; Male ; *Microsatellite Instability ; Middle Aged ; Phenotype ; Polymerase Chain Reaction ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Sensitivity and Specificity ; Sex Factors ; Stomach Neoplasms/*genetics/mortality

OBJECTIVETo study the morphologic and immunohistochemical features of gastrointestinal stromal tumors (GISTs) and to explore the reference parameters for malignancy.

METHODSSeventy six (76) cases of primary GISTs were distinguished from a group of gastrointestinal mesenchymal tumors by use of a panel of antibodies such as CD117, CD34 by immunohistochemical EnVision method, their biologic behaviors were analyzed by including their follow-up data.

RESULTSAll patients were adults, age range 32 to 81 years (mean 54 year), male 39 cases and female 37 cases; the tumors were situated in stomach (36 cases), in small intestine (23 cases), colon (2 cases) and rectum (15 cases). The most common symptoms were abdomen mass, vague pain and GI bleeding. Forty eight (48) cases were mainly located within the muscularis propria, 25 cases outside the serosa, and 3 cases below the mucosa. Grossly, they were of soft consistency often with hemorrhage, cystification or necrosis. Microscopically, the tumors were composed of spindle cells (46 cases) or epithelioid cells (9 cases) and of both cells (21 cases), arranged in interlacing fasicles, diffusing sheets, pallisading, whirling, alveolar and giant pseudo-rosette shapes. Tumor cells often had abundant cytoplasm with light to moderate eosinophilic or slight basophilic in staining, the nuclei generally showed spindle, blunted ends, round or signet in shape with nucleoli. Immunohistochemically, CD117 and CD34 showed diffuse strong expression, the positive rates were 98.7% and 68.4% respectively, alpha-SMA, MSA, S-100, PGP9.5 showed focal expression, the positive rates were 25.0%, 19.7%, 23.7% and 17.1% respectively, vimentin were all positive and desmin, GFAP, NF were all negative. Nine cases were benign, 19 cases borderline and 48 cases malignant. Follow-up of 20 cases with benign and borderline tumors found patients alive without tumor. In the malignant group of 34 cases, 10 cases were alive without tumor, 10 cases developed recurrence or metastasis, and 14 cases died of tumor. Coagulative necrosis, mitotic activity over 10/50HPF, high cellularity and obvious pleomorphism were all in the malignant group. In this group, tumor necrosis, adhesion in operation, tumor, over 5 cm in diameter, mitotic activity over 5/50HPF had significant differences among three groups and the 3 years survival rate had a significant difference in tumors with or without coagulative necrosis and also in tumors with or without mitotic activity over 5/50HPF.

CONCLUSIONSGISTs predominantly occurred in middle aged or old patients, the tumors had varied cell types and different arrangements, the immunohistochemical characters were positive for CD117 and CD34, negative for desmin, occasional positive for alpha-SMA, MSA, S-100 and PGP9.5, which were helpful to differentiate GIST from leiomyomas and Schwannomas. Coagulative necrosis, mitotic activity over 10/50HPF, high cellularity with obvious pleomorphism were also helpful parameters for diagnosis of malignancy aside from metastasis and invasion. Adhesion, over 5 cm in diameter and mitotic activity over 5/50HPF but less than 10/50HPF might be the potential malignant parameters.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Colonic Neoplasms ; metabolism ; pathology ; Female ; Gastrointestinal Neoplasms ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Intestinal Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Rectal Neoplasms ; metabolism ; pathology ; Statistics as Topic ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo investigate the expression of transcription factor Sp1 in gastric cancer tissue and its correlation with prognosis.

METHODSSp1 expression patterns in specimens of 86 gastric cancers, 57 normal gastric tissues and 53 metastatic lymph nodes were detected by immunohistochemical method. The activity of Sp1 in the tumor and normal tissues was examined by electrophoretic mobility shift analysis (EMSA). The correlation between transcription factor Sp1 expression of tumors and patients' prognosis were statistically analyzed using Cox proportional hazard model.

RESULTSIn normal gastric tissue, Sp1 protein was predominantly expressed in the nuclei of cell located in the mucous neck region, but neither in the gastric pit cells with foveolar differentiation, nor in cells of the glandular epithelium with glandular differentiation. Strong Sp1 expression was also detected in tumor cells, but very weak or even no Sp1 expression in stromal cells or normal glandular cells surrounding the tumor. The median survival time of patients with negative, weak, and strong Sp1 expression was 43, 37, and 8 months, respectively (P < 0.01). Spl expression (P < 0.01) and stage (P < 0.001) were demonstrated as independent prognostic factor by multivariate analysis.

CONCLUSIONNormal and malignant gastric tissue are found to have its own unique Sp1 expression patterns. Sp1 expression may be used as an important survival predictor in human gastric cancer.

Adenocarcinoma ; metabolism ; pathology ; Adenocarcinoma, Papillary ; metabolism ; pathology ; Biomarkers, Tumor ; metabolism ; Blotting, Western ; statistics & numerical data ; Cell Nucleus ; metabolism ; Electrophoretic Mobility Shift Assay ; Female ; Follow-Up Studies ; Gastric Mucosa ; chemistry ; pathology ; Humans ; Immunohistochemistry ; statistics & numerical data ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Sp1 Transcription Factor ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Survival Analysis

To investigate the correlations among total liver CT perfusion parameters, unpaired arteries (UAs) and microvessel area (MVA) in a rabbit liver VX2 tumor model, and to learn the tumoral angiogenesis condition and the mechanisms for perfusion imaging.
 Methods: Rabbits with or without the inoculated VX2 tumor in the liver underwent total liver CT perfusion imaging 2 weeks after the operation. Perfusion parameters included blood flow (BF), blood volume (BV), arterial liver perfusion (ALP), portal liver perfusion (PVP), hepatic perfusion index (HPI) for the tumor rim and the surrounding liver tissue. After the examination, the UAs and MVA of tumor tissues were obtained by immunohistochemical staining. The differences of perfusion parameters between the vital tumor rim and the surrounding liver tissue were compared. The correlations among perfusion parameters, UAs and MVA were analyzed.
 Results: There was significant difference between the CT perfusion parameters at the tumor rim and the surrounding liver tissue or liver tissue of the control group (P<0.05), but there was no significant difference between the perfusion parameters at the surrounding liver tissues of the experimental group and the control (P>0.05). There was positive correlation between UAs and MVA. UAs and MVA were positively correlated with BF, ALP and BV at the tumor rim. UAs and MVA were negatively correlated with PVP. HPI positively correlated with UAs, but it was not correlated with MVA.
 Conclusion: Total liver CT perfusion can provide quantitative information to evaluate the artery and portal vein perfusion of liver VX2 tumor, and to assess the degree of tumor angiogenesis.
Animals ; Arteries ; diagnostic imaging ; Blood Volume ; Carcinoma ; Immunohistochemistry ; Liver Circulation ; Liver Neoplasms ; blood supply ; diagnostic imaging ; Microvessels ; diagnostic imaging ; Neoplasm Transplantation ; Neoplasms, Squamous Cell ; Neovascularization, Pathologic ; diagnostic imaging ; Perfusion Imaging ; statistics & numerical data ; Portal System ; diagnostic imaging ; Rabbits ; Tomography, X-Ray Computed ; methods ; statistics & numerical data