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

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

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: 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

BACKGROUND/AIMS: Ribonucleotide reductase subunit M2 (RRM2) catalyzes the production of deoxynucleotide triphosphates, which are necessary for DNA synthesis. RRM2 has been reported to play an active role in tumor progression, and elevated RRM2 levels have been correlated with poor prognosis for colorectal cancer patients. This study aimed to elucidate the prognostic significance of RRM2 protein expression in hepatocellular carcinoma after surgery. METHODS: RRM2 protein expression was evaluated using immunohistochemistry in tumor tissues from 259 hepatocellular carcinoma patients who underwent curative hepatectomy. RESULTS: High RRM2 expression was observed in 210 of 259 patients (81.1%) with hepatocellular carcinomas. High RRM2 expression was significantly associated with viral etiology (p=0.035) and liver cirrhosis (p=0.036). High RRM2 expression was correlated with early recurrence (p=0.004) but not with late recurrence (p=0.144). Logistic regression analysis revealed that high RRM2 expression (p=0.040) and intrahepatic metastasis (p<0.001) were independent predictors of early recurrence. High RRM2 expression unfavorably influenced both shorter recurrence-free survival (p=0.011) and shorter disease-specific survival (p=0.002) and was an independent predictor of shorter disease-specific survival (p=0.008). CONCLUSIONS: High RRM2 protein expression might be a useful marker for predicting early recurrence and may be a marker for poor prognosis of hepatocellular carcinoma after curative hepatectomy.
Adolescent ; Adult ; Aged ; Carcinoma, Hepatocellular/*metabolism/surgery ; Disease-Free Survival ; Female ; Hepatectomy ; Humans ; Immunohistochemistry ; Liver Neoplasms/*metabolism/surgery ; Logistic Models ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*metabolism ; Prognosis ; Ribonucleoside Diphosphate Reductase/*metabolism ; Tumor Markers, Biological/*metabolism ; Young Adult

BACKGROUND/AIMS: Upregulation of aldo-keto reductase 1B10 (AKR1B10) through the mitogenic activator protein-1 signaling pathway might promote hepatocarcinogenesis and tumor progression. The goal of this study was to evaluate the prognostic significance of AKR1B10 protein expression in patients with hepatocellular carcinoma after surgery. METHODS: A tissue microarray was used to detect the expression level of AKR1B10 protein in tumors from 255 patients with hepatocellular carcinoma who underwent curative hepatectomy. The impact of AKR1B10 expression on the survival of patients was analyzed. The median follow-up period was 119.8 months. RESULTS: High AKR1B10 protein expression was observed in 125 of the 255 patients with hepatocellular carcinoma (49.0%). High AKR1B10 expression was significantly associated with a lack of invasion of the major portal vein (p=0.022), a lack of intrahepatic metastasis (p=0.010), lower the American Joint Committee on Cancer T stage (p=0.016), lower the Barcelona Clinic Liver Cancer stage (p=0.006), and lower alpha-fetoprotein levels (p=0.020). High AKR1B10 expression was also correlated with a lack of early recurrence (p=0.022). Multivariate analyses of survival revealed that intrahepatic metastases and lower albumin levels were independent predictors of both shorter recurrence-free survival and shorter disease-specific survival. High AKR1B10 expression was an independent predictor of both longer recurrence-free survival (p=0.024) and longer disease-specific survival (p=0.046). CONCLUSIONS: High AKR1B10 protein expression might be useful as a marker of a favorable prognosis in patients with hepatocellular carcinoma after curative hepatectomy.
Adolescent ; Adult ; Aged ; Aldehyde Reductase/*metabolism ; Carcinoma, Hepatocellular/*metabolism/surgery ; Disease-Free Survival ; Female ; Hepatectomy ; Humans ; Immunohistochemistry ; Liver Neoplasms/*metabolism/surgery ; Male ; Middle Aged ; Prognosis ; Tumor Markers, Biological/*metabolism ; Young Adult

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

PURPOSE: The aim of this study was to investigate the differences of expression in glycolysis-related proteins such as Glut-1, carbonic anhydrase (CA) IX, and monocarboxylate transporter (MCT) 4 according to the myoepithelial cell (MEC) and basement membrane (BM) status in solid papillary carcinoma (SPC) of the breast. MATERIALS AND METHODS: Immunohistochemical evaluation of Glut-1, CAIX, and MCT4, as well as p63 and type IV collagen, were performed on 23 SPC cases. RESULTS: Six and nine cases of SPC showed the presence and absence of myoepithelial cells, respectively, and eight cases belonged to the borderline status (p63-positive MEC on some areas of the outer tumor surface but not in others). BM was partially or completely absent in 14 cases and present in nine cases. SPC lacking BM more frequently showed high expression of CAIX than SPC with BM (p=0.037). CONCLUSION: In SPC of the breast, a strong expression of CAIX seems to be associated with an increasing degree of loss of BM, which can be interpreted as BM degradation due to the induction of extracellular acidity with increasing expression of CAIX.
Adult ; Aged ; Basement Membrane/*metabolism ; Breast Neoplasms/*metabolism ; Carcinoma, Papillary/*metabolism ; Excitatory Amino Acid Transporter 2/metabolism ; Female ; Glycolysis ; Humans ; Immunohistochemistry ; Middle Aged ; Monocarboxylic Acid Transporters/metabolism ; Muscle Proteins/metabolism ; Tumor Markers, Biological/*metabolism