PURPOSE: To compare the expression of survivin and its association with clinicopathological criteria in major types of urinary bladder carcinoma, specifically, transitional cell carcinoma with and without squamous differentiation and squamous cell carcinoma. MATERIALS AND METHODS: Immunohistochemical staining for survivin and Ki67 was performed on paraffin-embedded sections of 104 carcinomas: 52 transitional cell carcinoma, 20 transitional cell carcinoma with squamous differentiation, and 32 squamous cell carcinoma. Expression of survivin in >10% of tumor cells was described as altered survivin status. Ki67 staining in >20% of tumor cells was described as a high proliferation index. RESULTS: Altered survivin expression was detected in 60/104 specimens (58%) and was significantly more frequent in transitional cell carcinoma (78%) than in squamous cell carcinoma (38%) or transitional cell carcinoma with squamous differentiation (40%) (p<0.0001). In transitional cell carcinoma but not in squamous cell carcinoma, altered survivin status was associated with higher tumor grade, higher proliferation index, and recurrence. In the whole specimens, altered survivin expression was significantly associated with advanced stage (p<0.001), recurrence (p=0.005), distant metastasis (p<0.001), and death (p=0.001). In the multivariate analysis, altered survivin was an independent poor prognostic factor for recurrence. CONCLUSIONS: Unlike in transitional cell carcinoma, alteration of survivin expression in squamous cell carcinoma occurs less frequently and is not associated with features of tumor aggression or patient outcome. These findings raise a question: are urinary bladder carcinoma patients with squamous cell carcinoma type suitable candidates for survivin vaccine? This is an important question to be answered before approving the vaccine in management.
Carcinoma, Squamous Cell/*genetics ; Carcinoma, Transitional Cell/*genetics ; Female ; Humans ; Inhibitor of Apoptosis Proteins/genetics/*metabolism ; Ki-67 Antigen/metabolism ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Treatment Outcome ; Tumor Markers, Biological ; Urinary Bladder/pathology ; Urinary Bladder Neoplasms/*genetics

OBJECTIVE: Recent investigations have revealed DNA mismatch repair (MMR) gene mutations are closely related with carcinogenesis of endometrial cancer; however the impact of MMR protein expression on prognosis is not determined. Correlations between MMR-related protein expression and clinicopathological factors of endometrial cancers are analyzed in the present study. METHODS: A total of 191 endometrial cancer tissues treated between 1990 and 2007 in our hospital were enrolled. Immunoreactions for MSH2, MLH1, MSH6, and PMS2 on tissue microarray specimens and clinicopathological features were analyzed retrospectively. RESULTS: Seventy-six cases (40%) had at least one immunohistochemical alteration in MMR proteins (MMR-deficient group). There were statistically significant differences of histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and histological grade between MMR-deficient group and the other cases (MMR-retained group). Response rate of first-line chemotherapy in evaluable cases was slightly higher in MMR-deficient cases (67% vs. 44%, p=0.34). MMR-deficient cases had significantly better progression-free and overall survival (OS) compared with MMR-retained cases. Multivariate analysis revealed MMR status was an independent prognostic factor for OS in endometrial cancers. CONCLUSION: MMR-related proteins expression was identified as an independent prognostic factor for OS, suggesting that MMR was a key biomarker for further investigations of endometrial cancers.
Adaptor Proteins, Signal Transducing/deficiency/metabolism ; Adenosine Triphosphatases/deficiency/metabolism ; Adult ; Aged ; Aged, 80 and over ; Chemotherapy, Adjuvant ; *DNA Mismatch Repair ; DNA Repair Enzymes/deficiency/*metabolism ; DNA-Binding Proteins/deficiency/*metabolism ; Endometrial Neoplasms/*diagnosis/drug therapy/genetics/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; MutS Homolog 2 Protein/deficiency/metabolism ; Neoplasm Proteins/deficiency/metabolism ; Nuclear Proteins/deficiency/metabolism ; Prognosis ; Retrospective Studies ; Tumor Markers, Biological/*metabolism

No abstract available.
Biopsy ; Blood Glucose/metabolism ; C-Peptide/blood ; Calcium Gluconate/administration & dosage/*diagnostic use ; Female ; Humans ; Immunohistochemistry ; Injections, Intra-Arterial ; Insulin/blood ; Insulinoma/blood/*blood supply/pathology/surgery ; Middle Aged ; Pancreatic Neoplasms/blood/*blood supply/pathology/surgery ; Pancreaticoduodenectomy ; Splenic Artery/*radiography ; *Tomography, X-Ray Computed ; Treatment Outcome ; Tumor Markers, Biological/blood

No abstract available.
Adrenal Cortex Function Tests ; *Adrenal Cortex Neoplasms/complications/diagnosis/metabolism/surgery ; *Adrenal Gland Neoplasms/complications/diagnosis/metabolism/surgery ; Adrenalectomy ; *Adrenocortical Adenoma/complications/diagnosis/metabolism/surgery ; Biopsy ; Cushing Syndrome/diagnosis/etiology ; Female ; Humans ; Immunohistochemistry ; *Incidental Findings ; Middle Aged ; *Neoplasms, Multiple Primary/complications/diagnosis/metabolism/surgery ; *Pheochromocytoma/complications/diagnosis/metabolism/surgery ; Predictive Value of Tests ; Tomography, X-Ray Computed ; Treatment Outcome ; Tumor Markers, Biological/metabolism

BACKGROUND/AIMS: Protein disulfide isomerase (PDI) has been implicated in the survival and progression of some cancer cells, by compensating for endoplasmic reticulum stress by upregulating the protein-folding capacity. However, its prognostic role in patients with hepatocellular carcinoma (HCC) has not been investigated. METHODS: We collected HCC tissues from 83 HCC patients who underwent surgical resection for an immunohistochemical study of PDI. Overall survival (OS) was measured from the date of surgical resection until the date of death from any cause. Radiological progression was evaluated using the modified Response Evaluation Criteria in Solid Tumors in an independent radiological assessment. RESULTS: PDI expression was found to be increased in human HCC compared to adjacent nontumor tissues. Increased immunopositivity for PDI was associated with a high Edmondson-Steiner grade (p = 0.028). Univariate analysis of patients who had undergone surgical resection for HCC showed that tumor PDI upregulation is a significant risk factor for poor OS (p = 0.016; hazard ratio [HR], 1.980) and time to progression (TTP; p = 0.007; HR, 1.971). Multivariate analyses revealed that high PDI expression was an independent predictor of a shorter TTP (p = 0.015; HR, 1.865) and poor OS (p = 0.012; HR, 2.069). CONCLUSIONS: Upregulated PDI expression is associated with aggressive clinicopathological features of HCC; thus, PDI might serve as an independent prognostic factor and a potential therapeutic target for HCC patients.
Carcinoma, Hepatocellular/*enzymology/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/*enzymology/pathology ; Male ; Middle Aged ; Prognosis ; Protein Disulfide-Isomerases/*metabolism ; Retrospective Studies ; Tumor Markers, Biological/metabolism

BACKGROUND/AIMS: Epithelial-mesenchymal transition (EMT)-related proteins may exhibit differential expression in intestinal type or pancreatobiliary type ampulla of Vater carcinomas (AVCs). We evaluated the expression of E-cadherin, beta-catenin, and S100A4 in intestinal and nonintestinal type AVCs and analyzed their relationships with clinicopathological variables and survival. METHODS: A clinicopathological review of 105 patients with AVCs and immunohistochemical staining for E-cadherin, beta-catenin, and S100A4 were performed. The association between clinicopathological parameters, histological type, and expression of EMT proteins and their effects on survival were analyzed. RESULTS: Sixty-five intestinal type, 35 pancreatobiliary type, and five other types of AVCs were identified. The severity of EMT changes differed between the AVC types; membranous loss of E-cadherin and beta-catenin was observed in nonintestinal type tumors, whereas aberrant nonmembranous beta-catenin expression was observed in intestinal type tumors. EMT-related changes were more pronounced in the invasive tumor margin than in the tumor center, and these EMT-related changes were related to tumor aggressiveness. Among the clinicopathological parameters, a desmoplastic reaction was related to overall survival, and the reaction was more severe in nonintestinal type than in intestinal type AVCs. CONCLUSIONS: Dysregulation of E-cadherin, beta-cadherin, and S100A4 expression may play a role in the carcinogenesis and tumor progression of AVCs.
Aged ; Aged, 80 and over ; Ampulla of Vater/*metabolism ; Cadherins/metabolism ; Common Bile Duct Neoplasms/classification/*metabolism ; Disease-Free Survival ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; S100 Proteins/metabolism ; Tumor Markers, Biological/*metabolism ; beta Catenin/metabolism

BACKGROUND/AIMS: The current study examines the expression of molecular biomarkers in hepatocellular carcinoma (HCC) and whether these findings correlate with the clinicopathologic features of the disease and patient survival. METHODS: We analyzed the immunohistochemical expression of p53, mammalian target of rapamycin (mTOR), c-Met, and insulin-like growth factor 1 receptor (IGF-1R) heat shock protein 70 (HSP70) with the clinicopathologic features of 83 HCCs. RESULTS: p53 expression was higher in the male patients with undifferentiated histological tumor grades, cirrhosis, and portal vein invasion. High 48 c-Met expression correlated with cirrhosis, and high mTOR expression correlated with the tumor grade and cirrhosis. High IGF-1R expression correlated with the tumor grade and cirrhosis. A multivariate analysis identified a significant relationship between the high expression of p53, tumor grade, and portal vein invasion. In addition, a high expression of mTOR was related to tumor grade and cirrhosis, and a high expression of HSP70 was related to portal vein invasion in a multivariate analysis. The Kaplan-Meier survival curve for patients with high versus low Edmondson grades and p53 expression was statistically significant. CONCLUSIONS: p53, mTOR, and IGF-1R expression correlated with the Edmondson tumor grade in a univariate analysis, while p53 and mTOR correlated with the Edmondson tumor grade in a multivariate analysis. In addition, the tumor grade was found to predict survival. p53 was primarily related to the clinicopathologic features compared to other markers, and it is a poor prognostic factor of survival.
Adult ; Aged ; Carcinoma, Hepatocellular/*metabolism/surgery ; Disease-Free Survival ; Female ; HSP70 Heat-Shock Proteins/metabolism ; Humans ; Liver Neoplasms/*metabolism/surgery ; Male ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins c-met/metabolism ; Receptor, IGF Type 1/metabolism ; Retrospective Studies ; Risk Factors ; TOR Serine-Threonine Kinases/metabolism ; Treatment Outcome ; Tumor Markers, Biological/*metabolism ; Tumor Suppressor Protein p53/metabolism

PURPOSE: Autophagy has been reported to be involved in treatment failure in tumor. We aimed to evaluate autophagy activity in tumor tissue and compare them between the recurrence and non-recurrence groups. MATERIALS AND METHODS: We analyzed expressions of autophagy-related proteins in tumor tissues which were obtained from pulmonary metastases of colorectal cancer patients by Western blot. We also analyzed autophagosomes by transmission electron microscopy. RESULTS: Tumor tissues from recurrence group showed increased levels of LC3B-II, decreased levels of p62/SQSTM1, and also a marked accumulation of autophagosomes compared with tissues from non-recurrence group. CONCLUSION: The present study suggests that autophagy may be associated with treatment failure of metastatic colorectal cancer.
Adaptor Proteins, Signal Transducing ; Aged ; *Autophagy ; Blotting, Western ; Colorectal Neoplasms/*metabolism/*pathology ; Female ; Humans ; Lung Neoplasms/*metabolism/*pathology ; Male ; Microfilament Proteins/*metabolism ; Microscopy, Electron, Transmission ; Microtubule-Associated Proteins ; Middle Aged ; Neoplasm Recurrence, Local ; Pilot Projects ; Proteins ; Retrospective Studies ; Treatment Failure ; Tumor Markers, Biological/metabolism

BACKGROUND/AIMS: Oxidative stress increases the risk of cardiovascular complications of metabolic syndrome (MetS). This study was conducted to examine the difference in antioxidant capacity according to the presence of MetS, and to characterize the association between antioxidant capacity and MetS-related factors. METHODS: We used the biological antioxidant potential (BAP) test to estimate antioxidant capacity. The BAP test has recently been used as an indicator of antioxidant capacity. We measured BAP levels in 45 patients with MetS (mean age, 44.6 +/- 1.1 years) and 47 age- and sex-matched controls (mean age, 42.7 +/- 1.1 years). To evaluate the association between antioxidant capacity and MetS, adiponectin, high-sensitivity C-reactive protein (hs-CRP), interleukin-6, tumor necrosis factor-alpha, and homeostatic model assessment for insulin resistance (HOMA-IR), linear regression and logistic analyses were performed. RESULTS: The mean BAP of the MetS group (1,937.3 +/- 36.5 micromol/L) was significantly lower than that of the non-MetS group (2,101.7 +/- 29.5 micromol/L). Also, the mean BAP was low in persons having low high density lipoprotein and high triglyceride. Reduced antioxidant capacity was significantly associated with adiponectin, HOMA-IR and hs-CRP after adjusting for age and sex. The odds ratios for MetS with BAP, log adiponectin, log HOMA-IR, and log hs-CRP were 0.63 (95% confidence interval [CI], 0.49 to 0.82), 0.22 (0.10 to 0.51), 14.24 (4.35 to 46.58), and 1.93 (1.36 to 2.75), respectively. CONCLUSIONS: Persons with MetS showed reduced antioxidant capacity. We identified relationships between antioxidant capacity measured by BAP test and MetS, as well as MetS-related factors, such as insulin resistance, hs-CRP, and adiponectin.
Adipokines/blood ; Adult ; Antioxidants/*metabolism ; Biological Markers/blood ; C-Reactive Protein/metabolism ; Case-Control Studies ; Female ; Humans ; Insulin Resistance ; Interleukin-6/blood ; Male ; Metabolic Syndrome X/*blood ; Middle Aged ; Predictive Value of Tests ; Tumor Necrosis Factor-alpha/blood

No abstract available.
Antigens, Neoplasm/*metabolism ; Antineoplastic Agents/*therapeutic use ; Cell Adhesion Molecules/*metabolism ; Female ; Humans ; Neoplasms, Glandular and Epithelial/*diagnosis ; Organoplatinum Compounds/*therapeutic use ; Ovarian Neoplasms/*diagnosis ; Tumor Markers, Biological/*metabolism