OBJECTIVETo investigate the expression of calcyclin in pancreatic carcinoma and its relation to the patients' prognosis.

METHODSHuman pancreatic carcinoma tissue microarray was constructed, which contained 63 cores of 3 normal adult pancreas tissues, 6 chronic pancreatitis tissues, 51 pancreatic carcinoma tissues and 3 islet cell carcinoma tissues. Immunohistochemistry was performed to detect the expression of calcyclin in these tissues, and the relationship between calcyclin and the clinicopatholoical features of pancreatic carcinoma was analyzed.

RESULTSThe positivity rate of calcyclin in the pancreatic carcinoma tissue was 76.5% (39/51), and calcyclin staining was more intense in the malignant cells than in the benign cells (P=0.007), suggesting a correlation between calcyclin expression and pancreatic carcinoma. No evidence was found for an association of calcyclin expression with the variables including the patients' gender, age at surgery, and tumor grade. Weak staining for calcyclin was noted in chronic pancreatitis tissues.

CONCLUSIONCalcyclin expression is related to the pancreatic carcinomas and up-regulation of calcyclin expression is possibly an early event in pancreatic and pragression of development cancer.

Adult ; Aged ; Biomarkers, Tumor ; genetics ; metabolism ; Cell Cycle Proteins ; genetics ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Pancreatic Neoplasms ; genetics ; metabolism ; Pancreatitis, Chronic ; genetics ; metabolism ; S100 Calcium Binding Protein A6 ; S100 Proteins ; genetics ; metabolism

Integrative genetic changes were examined in relation to tumor growth and progression of sporadic colorectal cancers. Ninety-two sporadic colorectal cancer patients and 12 human colorectal cancer cell lines were evaluated. Genetic changes in representative steps of colorectal tumorigenesis were determined. Biological characteristics, i.e., clinicopathologic parameters, expression of invasion-associated molecules, and in vitro invasion and migration, in association with these changes were further analyzed. Adenomatous polyposis coli (APC) and/or Wnt-activated alterations occurred in 66% patients, whereas mismatch repair (MMR) defects and/or RAF-mediated alterations were identified in 47% patients. The crossover rate between these two alterations was 26%. Differential mRNA expression of ARK5 was closely associated with that of MMP2, MMP9, and S100A4 (P< or =0.044-0.001). Additionally, enhanced ARK5 mRNA expression was more frequent in tumors displaying RAF-mediated alterations and crossover pathways (P=0.01 and 0.03, respectively). Upregulation of CEA mRNA was more common in the advanced stages (P=0.034), while VEGF expression was greater in poorly differentiated or mucinous tumors (P=0.042). The high expressions of MMP2 and MMP9 were closely associated with invasion and migration of colorectal tumors and cell lines. Our results conclusively show that specific pathways of colorectal tumorigenesis are closely associated with characteristic tumor growth and invasion.
*Adenocarcinoma/genetics/metabolism/pathology ; Animals ; Carcinoembryonic Antigen/genetics/metabolism ; Cell Line, Tumor ; Cell Movement ; *Colorectal Neoplasms/genetics/metabolism/pathology ; *Gene Expression Regulation, Neoplastic ; Humans ; Matrix Metalloproteinase 2/genetics/metabolism ; Matrix Metalloproteinase 9/genetics/metabolism ; Neoplasm Invasiveness ; Protein Kinases/genetics/metabolism ; Repressor Proteins/genetics/metabolism ; S100 Proteins/genetics/metabolism ; Vascular Endothelial Growth Factor A/genetics/metabolism

OBJECTIVEPancreatic cancer is one of the most deadly cancers, which is characterized by its high metastatic potential. S100A4 is a major prometastatic protein involved in tumor invasion and metastasis which precise role in pancreatic cancer has not been fully investigated. We knocked down the S100A4 gene in the Bxpc-3 pancreatic cancer cell line via RNA interference to study the changes in cell behavior.

METHODSReal-time polymerase chain reaction and western blotting were used to detect mRNA and protein expression levels of S100A4, matrix metalloproteinase (MMP)-2, E-cadherin and thrombospondin (TSP)-1. Transwell chambers were used to detect the migration and invasion abilities; a cell adhesion assay was used to detect adhesion ability; colony forming efficiency was used to detect cell proliferation; flow cytometry was used to detect apoptosis.

RESULTSS100A4 mRNA expression was reduced to 17% after transfection with S100A4-siRNA, and protein expression had a similar trend. mRNA and protein expression of MMP-2 was reduced and that of E-cadherin and TSP-1 was elevated, indicating that S100A4 affects their expression. S100A4-silenced cells exhibited a marked decrease in migration and invasiveness and increased adhesion, whereas overall proliferation and apoptosis were not overtly altered.

CONCLUSIONS100A4 and its downstream factors play important roles in pancreatic cancer invasion, and silencing A100A4 can significantly contain the invasiveness of pancreatic cancer.

Apoptosis ; genetics ; physiology ; Blotting, Western ; Cadherins ; genetics ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Pancreatic Neoplasms ; genetics ; metabolism ; RNA Interference ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; S100 Calcium-Binding Protein A4 ; S100 Proteins ; genetics ; metabolism ; Thrombospondin 1 ; genetics ; metabolism

Adenoma ; genetics ; metabolism ; pathology ; surgery ; Adult ; Carcinoma, Renal Cell ; genetics ; metabolism ; pathology ; Chromosomes, Human, Pair 3 ; genetics ; Chromosomes, Human, Pair 7 ; genetics ; Diagnosis, Differential ; Diploidy ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Retrospective Studies ; S100 Proteins ; metabolism ; Vimentin ; metabolism ; WT1 Proteins ; metabolism ; Wilms Tumor ; metabolism ; pathology

Age Factors ; Child ; Child, Preschool ; Ganglioneuroblastoma ; genetics ; metabolism ; pathology ; ultrastructure ; Ganglioneuroma ; genetics ; metabolism ; pathology ; ultrastructure ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; Infant ; N-Myc Proto-Oncogene Protein ; Neoplasm Staging ; Neuroblastoma ; genetics ; metabolism ; pathology ; ultrastructure ; Nuclear Proteins ; genetics ; metabolism ; Oncogene Proteins ; genetics ; metabolism ; Peripheral Nervous System Neoplasms ; classification ; genetics ; metabolism ; pathology ; ultrastructure ; Prognosis ; Proto-Oncogene Proteins c-myc ; metabolism ; Receptor, trkA ; metabolism ; S100 Proteins ; metabolism

Several pathologic characteristics are associated with an adverse clinical outcome in papillary thyroid carcinoma (PTC), including the histological variant. This study aimed to investigate immunohistochemical expression and BRAF mutation status based on the histological variant and evaluated potential markers of aggressive behavior of PTC in Korean patients. In all, 407 PTC cases were classified to each histological variant, and the 94 representative cases were subjected to immunohistochemistry and BRAF mutation analysis. The classic type, follicular variant (FV) and tall cell variant (TCV) represented 76.9%, 14.2% and 6%, respectively. TCV showed a larger tumor size (P = 0.009), frequent extrathyroidal extension (P = 0.022) and cervical lymph node (LN) metastasis (P = 0.018). TCV and FV showed the reduced expression of galectin-3 (P = 0.003) and HBME1 (P = 0.114). Regardless of histology, PTEN loss and diffuse S100A4 expression were associated with LN metastasis (P = 0.007, P = 0.013). All TCVs harbored BRAF V600E mutation, and FV harbored less BRAF V600E mutation (P = 0.043). Immunohistochemical evaluation showed characteristic patterns in histological variants. PTEN and S100A4 expression are suggested as indicators of regional lymph node metastasis.
Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/*genetics ; Carcinoma, Papillary/genetics/metabolism/*pathology ; DNA Mutational Analysis ; Exons ; Female ; Galectin 3/metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Mutation ; PTEN Phosphohydrolase/metabolism ; Proto-Oncogene Proteins B-raf/*genetics/metabolism ; Republic of Korea ; S100 Proteins/metabolism ; Thyroid Neoplasms/genetics/metabolism/*pathology ; Tumor Markers, Biological/metabolism ; Young Adult

OBJECTIVETo investigate the regulation mechanism of apoptosis induced by the antisense bcl-2 treatment.

METHODSDNA content analysis and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) were adopted to detect apoptosis. Semi-quantitative reverse transcription-PCR was performed to detect the mRNA expression of bcl-2 c-myc survivin bax s100A(2) TNFalpha TGFbeta(1) and IL-6 in the small-cell lung cancer cell line NCI-H446 treated with antisense bcl-2 oligodeoxynucliotide.

RESULTSbcl-2 AS-PS-ODN treatment could induce apoptosis, accompanied with 72.71% up-regulation of IL-6 and 65.90% down-regulation of TNFalpha, whereas little or no effect was seen on c-myc survivin bax s100A(2) and TGFbeta(1).

CONCLUSIONIL-6 and TNFalpha may be involved in the regulation of apoptosis induced by antisense bcl-2 treatment.

Apoptosis ; drug effects ; genetics ; Chemotactic Factors ; genetics ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; In Situ Nick-End Labeling ; Inhibitor of Apoptosis Proteins ; Interleukin-6 ; genetics ; Microtubule-Associated Proteins ; genetics ; Neoplasm Proteins ; Oligonucleotides, Antisense ; pharmacology ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; Proto-Oncogene Proteins c-myc ; genetics ; RNA, Messenger ; drug effects ; genetics ; metabolism ; S100 Proteins ; genetics ; Transforming Growth Factor beta ; genetics ; Transforming Growth Factor beta1 ; Tumor Cells, Cultured ; drug effects ; Tumor Necrosis Factor-alpha ; genetics ; bcl-2-Associated X Protein

OBJECTIVETo study the clinicopathologic features and differential diagnosis of proximal gastric mucosa and mucosa of Barrett's esophagus (BE) in biopsy specimens.

METHODThirty-eight cases of Barrett's esophagus (diagnosed using WHO criteria) and 44 cases of proximal gastric mucosa were studied by immunohistochemistry (for CK7, CK20, CK4, CK8, S-100 protein, MUC6, COX2 and bcl-2) and fluorescence in-situ hybridization (FISH) (for hTERC gene). The pathologic features were analyzed.

RESULTSThe differences in expression of CK7, CK20, MUC6, COX2 and bcl-2 between BE and proximal gastric mucosa with intestinal metaplasia were not statistically significant (P > 0.05). There was however a statistically significant difference in expression of S-100 protein (P < 0.05). The expression of CK7/CK4 and CK7/CK8 in BE showed positive correlation (P < 0.05). However, such correlation was not demonstrated in proximal gastric mucosa (P > 0.05). The results of hTERC gene expression by FISH showed a statistically significant difference between the two groups: 57.9% (22/38) in BE and 13.6% (6/44) in proximal gastric mucosa (P < 0.05).

CONCLUSIONSThe significance of CK7 and CK20 expression is uncertain in the differential diagnosis between BE and proximal gastric mucosa. On the other hand, positivity for CK7/CK4/CK8 may support the diagnosis of BE and play a role in distinguishing between the two groups. S-100 protein expression and detection of hTERC gene amplification also contribute to the diagnosis of BE.

Barrett Esophagus ; genetics ; metabolism ; pathology ; Gastric Mucosa ; metabolism ; pathology ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Keratin-20 ; metabolism ; Keratin-4 ; metabolism ; Keratin-7 ; metabolism ; Keratin-8 ; metabolism ; Metaplasia ; genetics ; metabolism ; pathology ; RNA ; genetics ; Retrospective Studies ; S100 Proteins ; metabolism ; Telomerase ; genetics

OBJECTIVETo explore the role of S100A4 in the epithelial-mesenchymal transition (EMT) in esophageal squamous cell carcinoma and its possible molecular mechanism.

METHODSThree chemically synthesized S100A4 siRNA sequences were transiently transfected into esophageal carcinoma EC9706 cells. EC9706 cells transfected with negative siRNA, lipofectamine 2000, and vacant EC9706 cells were used as control. Fluorescence quantitative RT-PCR and Western blot were used to detect the inhibition rate of S100A4 siRNA. S100A4 siRNA2 with the best inhibition rate was chosen to transiently transfect into EC9706 cells under the same conditions. The EC9706 cells transfected with negative siRNA, lipofectamine 2000 and vacant EC9706 cells were also used as control. Fluorescence quantitative RT-PCR and Western blot were used to detect the mRNA and protein expressions of E-cadherin, vimentin and snail. The morphology of EC9706 cells was observed under an inverted microscope. Boyden chamber and scratch test were used to detect the invasion and migration ability of EC9706 cells, and CCK8 assay was used to detect the proliferation ability of EC9706 cells. EC9706 cells transfected with S100A4 siRNA2 were further transfected with snail eukaryotic expression vector. The EC9706 cells transfected with S100A4 siRNA, EC9706 cells transfected with snail eukaryotic expression vector and vacant EC9706 cells were used as control. The above indexes of all the groups were observed, too.

RESULTSThe S100A4 mRNA and protein expression levels of the S100A4 siRNA2 group were 0.417 ± 0.041 and 0.337 ± 0.039, the transmembrane cell number was 61.608 ± 8.937, the scratch healing distance was (0.216 ± 0.064) mm, the A value was 0.623 ± 0.084, the E-cadherin mRNA and protein levels were 0.619 ± 0.032 and 0.495 ± 0.034, the vimentin mRNA and protein levels were 0.514 ± 0.032 and 0.427 ± 0.028, the snail mRNA and protein levels were 0.573 ± 0.029 and 0.429 ± 0.041. These data were significantly different with the liposome group, the negative control group and the blank group (P < 0.05 for all). After the S100A4 siRNA2 treatment for 24 h, the appearance of EC9706 cells changed to epithelial cell morphology. The transmembrane cell number and the scratch healing distance of the S100A4 siRNA2+snail eukaryotic expression vector group were (69.382 ± 9.666) cells and (0.274 ± 0.029) mm, the A value was 0.823 ± 0.101, the snail mRNA and protein levels were 0.704 ± 0.037 and 0.625 ± 0.031, the vimentin mRNA and protein levels were 0.712 ± 0.046 and 0.609 ± 0.038, and these data were significantly higher than those of the Sl00A4 siRNA2 group (P < 0.05 for all). The E-cadherin mRNA and protein levels of the S100A4 siRNA2+eukaryotic expression vector group were 0.437 ± 0.038 and 0.381 ± 0.031, significantly lower than those of the S100A4 siRNA2 group (P < 0.05 for all). However, snail had no effect on the morphology of EC9706 cells.

CONCLUSIONSS100A4 may be involved in the EMT process of esophageal squamous-cell carcinoma by regulating the expression of snail and then plays a role in the invasion and metastasis of esophageal carcinoma.

Cadherins ; analysis ; Carcinoma, Squamous Cell ; metabolism ; pathology ; physiopathology ; Cell Line, Tumor ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Esophageal Neoplasms ; metabolism ; pathology ; physiopathology ; Humans ; Indicators and Reagents ; Lipids ; RNA, Messenger ; analysis ; RNA, Small Interfering ; analysis ; physiology ; S100 Calcium-Binding Protein A4 ; S100 Proteins ; antagonists & inhibitors ; genetics ; physiology ; Snail Family Transcription Factors ; Transcription Factors ; analysis ; genetics ; Transfection ; Vimentin ; analysis ; genetics

OBJECTIVETo study the clinicopathological features, immunophenotype, differential diagnosis and prognosis of low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA).

METHODSThe histopathological features and clinical and pathological data of nine cases of LGNPPA were retrospectively analyzed. Immunohistochemistry (Two-step EnVision methods) was used to evaluate the expression of CKpan, vimentin, CK7, CK19, TTF-1 and TG; in situ hybridization was used to detect Epstein-Barr virus mRNA (EBER); and flow-through hybridization was used to evaluate the presence of human papilloma virus (HPV).

RESULTSThe mean age for the nine patients (eight males, one female) was 45.3 years (range 23 to 62 years). Microscopically the tumors were characterized by lobulated, papillary and glandular structures with patchy distribution of spindle cells. The papillary interstitial tissue was edematous, myxoid or hyalinized. The tumors were unencapsulated and infiltrated into the surrounding stroma. Four cases displayed transition between normal nasopharyngeal epithelium to neoplastic cells; and one case contained psammoma bodies. Five cases were strongly positive for CKpan, vimentin, CK7, CK19, TTF-1, and were focally positive for EMA and CD117. These five cases were all negative for TG, CK5/6, CK20, S-100 protein, p63, Calponin and SMA. In situ hybridization for EBER and flow-through hybridization for HPV were negative in all five cases. Follow-up data showed no post-operative recurrence of the LGNPPA.

CONCLUSIONSLGNPPA is a rare low-grade neoplasm with distinct morphological characteristics. Its diagnosis is primarily based on the site of lesions and the histological features. The diagnosis and differential diagnosis of LGNPPA could be aided by immunohistochemical staining. LGNPPA may originate from nasopharyngeal epithelium; and the prognosis is good with simple and complete resection.

Adenocarcinoma, Papillary ; metabolism ; pathology ; Adult ; Carcinoma ; Diagnosis, Differential ; Female ; Herpesvirus 4, Human ; genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Male ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Proteins ; metabolism ; Nuclear Proteins ; metabolism ; Prognosis ; RNA, Messenger ; metabolism ; Retrospective Studies ; S100 Proteins ; metabolism ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism ; Vimentin ; metabolism