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

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

The transforming growth factor β1 (TGF-β1) and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130 (stage I-III) invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival (DDFS) (HR=8.416, 95% CI=1.636-43.292, P=0.011) in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival (OS) than their counterparts with CD8-positive cell infiltration into tumor nests (Log-Rank, P=0.003). But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy (Log-Rank, P=0.013) and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor (t-TGF-β1-pre)-positive patients than in the negative patients in patients without receiving chemotherapy (P=0.053), OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy (P=0.035) and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS (HR=0.392 95% CI=0.157-0.978, P=0.045) in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.
Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; drug therapy ; metabolism ; surgery ; CD8-Positive T-Lymphocytes ; metabolism ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Outcome Assessment (Health Care) ; methods ; statistics & numerical data ; Prognosis ; Proportional Hazards Models ; Protein Precursors ; metabolism ; Retrospective Studies ; Transforming Growth Factor beta1 ; metabolism

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

OBJECTIVETo investigate the expression of cysteine-rich protein 61 (Cyr61) and NF-kappaB in gastric carcinoma and its correlation with the clinicopathologic features and survival time.

METHODSRT-PCR was used to validate and detect expression of Cyr61 mRNA in 53 gastric carcinoma specimens and 11 non-tumor gastric mucosa samples. Cyr61 and NF-kappaB protein levels expressed were detected using immunohistochemistry in 99 gastric carcinoma specimens and 25 non-tumor gastric mucosa samples.

RESULTSRT-PCR demonstrated that expression of Cyr61 mRNA was higher in the primary carcinoma (84.6%, 22/26) and the metastatic foci (88.9%, 24/27) than in the non-tumor control samples (5/11; P < 0.05, respectively). Cyr61 gene mRNA expression levels were (2.76 +/- 5.50) x 10(-5), (14.61 +/- 20.64) x 10(-5), and (18.46 +/- 26.38) x 10(-5) by 2(-DeltaCt) in the control mucosa samples, primary carcinomas and metastatic tissues respectively. The level was higher in the primary carcinomas and metastatic tissues than that of the non-tumor gastric mucosa (P < 0.05, respectively); however, there was no significant difference between the metastatic tissues and the primary carcinomas (P > 0.05). Immunohistochemistry revealed that of the 99 cases, there was a high expression of Cyr61 and NF-kappaB protein, 56.6% (56/99) and 55.6% (55/99) respectively. There was correlation of Cyr61 and NF-kappaB protein expressions with the depth of tumor and vascular invasion, as well as the development of lymph node metastasis, and TNM staging (P < 0.05, respectively), besides, the expression of NF-kappaB also correlated with the tumor diameter (P < 0.05). Cyr61 expression was positively correlated with NF-kappaB expression in gastric carcinoma (P < 0.05); the mean survival time in cases with a high expression level of Cyr61 and NF-kappaB protein was significantly shorter than those with a low expression level (P < 0.05).

CONCLUSIONSExpression of Cyr61 and NF-kappaB closely correlated with invasion and metastasis of gastric carcinoma. They may be considered as the biologic behavior indicators for gastric carcinoma.

Carcinoma ; genetics ; metabolism ; Cysteine-Rich Protein 61 ; genetics ; metabolism ; Female ; Gastric Mucosa ; pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; diagnosis ; genetics ; Male ; NF-kappa B ; genetics ; metabolism ; Neoplasm Staging ; Prognosis ; Statistics as Topic ; Stomach Neoplasms ; diagnosis ; genetics ; metabolism ; Treatment Outcome

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

AIMTo investigate human epidermal growth factor receptor type 2 (HER2) protein expression and gene amplification in Chinese metastatic prostate cancer patients and their potential value as prognostic factors.

METHODSImmunohistochemistry (IHC) was performed to investigate HER2 protein expression in prostate biopsy specimens from 104 Chinese metastatic prostate cancer patients. After 3-11 months of hormonal therapy, 12 patients underwent transurethral resection of the prostate (TURP). HER2 protein expression of TURP specimens was compared with that of the original biopsy specimens. Of these, 10 biopsy and 4 TURP specimens with HER2 IHC staining scores >or=2+ were investigated for HER2 gene amplification status by fluorescent in situ hybridization (FISH).

RESULTSOf the 104 prostate biopsy specimens, HER2 protein expression was 0, 1+, 2+ and 3+ in 49 (47.1%), 45 (43.3%), 8 (7.7%) and 2 (1.9%) cases, respectively. There was a significant association between HER2 expression and Gleason score (P = 0.026). HER2 protein expression of prostate cancer tissues increased in 33.3% of patients after hormonal therapy. None of the 14 specimens with HER2 IHC scores >or= 2+ showed HER2 gene amplification. Patients with HER2 scores >or= 2+ had a significantly higher chance of dying from prostate cancer than those with HER2 scores of 0 (P = 0.004) and 1+ (P = 0.034). Multivariate Cox regression analysis showed that HER2 protein expression intensity was an independent predictor of cancer-related death (P = 0.039).

CONCLUSIONAn HER2 IHC score >or= 2+ should be defined as HER2 protein overexpression in prostate cancer. Overexpression of HER2 protein in cancer tissue might suggest an increased risk of dying from prostate cancer. HER2 protein expression increases in some individual patients after hormonal therapy.

Aged ; Antineoplastic Agents, Hormonal ; therapeutic use ; Asian Continental Ancestry Group ; genetics ; statistics & numerical data ; Biopsy ; China ; epidemiology ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Prostatic Neoplasms ; drug therapy ; genetics ; mortality ; secondary ; Receptor, ErbB-2 ; genetics ; metabolism ; Risk Factors

OBJECTIVETo study the relationship between clinicopathological and biological characteristics and prognosis in young females with breast cancer.

METHODSThe clinicopathological data of 99 young patients (< or =35years) with primary breast cancer were analyzed retrospectively. All the 99 patients were followed up for 5 years. The histological specimens were reviewed. The expression of ER, PR, AR, c-erbB2, ki67, p53 and BRCA1 were assessed by immunohistochemistry in 63 carcinomas.

RESULTSThe lymph node involvement, 5-year metastasis and 5-year survival rate were 59.6% (59/99), 28.0% (26/ 93) and 72.7% (72/99), respectively. The univariate analysis showed that the survival was related to lymphatic vessel invasion, fat involvement, node-positive status, EIC, AR and c-erbB2 expression. The COX multivariate analysis identified that only node-positive status, AR negativity and c-erbB2 overexpression were independent prognostic factors.

CONCLUSIONOur data demonstrated that the lymph node status and c-erbB2 expression are strong prognostic factors in young patients with breast cancer. AR may be an adjuvant prognostic factor. The therapeutic measurement could not benefit the outcome radically.

Adult ; Biomarkers, Tumor ; analysis ; Breast Neoplasms ; metabolism ; mortality ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; statistics & numerical data ; Ki-67 Antigen ; analysis ; Lymphatic Metastasis ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2 ; analysis ; Receptors, Androgen ; analysis ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Survival Analysis ; Survival Rate ; Tumor Suppressor Protein p53 ; analysis

OBJECTIVETo analyze the clinicopathological features, parameters of molecular biology, survival rate, and prognostic factors in breast cancer patients with vascular invasion.

METHODSThe data of 262 breast cancer patients with vascular invasion surgically treated between January 1995 and December 2003 in our institution were retrospectively analyzed. Clinicopathological characteristics, parameters of molecular biology, disease free survival rate and overall survival rate were surveyed.

RESULTSOf all breast cancer patients registered in our institution during the same period, these 262 breast cancer patients with vascular invasion accounted for 5.3% with a median age of 43 years. The major pathological type was invasive ductal carcinoma (93.3%). The stages included stage I in 5% , stage II 31. 3% , stage III 58.8% , stage IV 1.1% , and unknown 3.8%. Immunohistochemical staining showed that ER positive in 67.7%, PR(+) 68.0%, p53(+) 54.2%, PCNA(+) 93.3%, c-erbB2( +++) 20.8% and c-erbB2(++) 16.9%. The 5-year and 10-year cumulative disease free survival and overall survival were 57.6% , 50.7% and 62.8%, 52.9% , respectively. The factors which were found to compromise disease free survival were the tumor size, lymph node status, stage, and radiotherapy in the univariate analysis, and for overall survival, were the tumor size, lymph node status, stage, location of vascular invasion and radiotherapy. The tumor size and radiotherapy were found to be independent prognostic factors for disease free survival and overall survival in the multivariate analysis.

CONCLUSIONBreast cancers with vascular invasion have poor biological behavior though having been treated by surgery, radiotherapy and chemotherapy. The independent prognostic factors of such patients are tumor size and radiotherapy. Anti-angiogenesis and antilymphangiogenesis may gradually become promising target treatment for such patient.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; metabolism ; pathology ; therapy ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; therapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; statistics & numerical data ; Lymphatic Metastasis ; Mastectomy ; methods ; Middle Aged ; Neoplasm Staging ; Neoplastic Cells, Circulating ; metabolism ; pathology ; Prognosis ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Tumor Suppressor Protein p53 ; metabolism

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