Identification of PTPRR and JAG1 as key genes in castration-resistant prostate cancer by integrated bioinformatics methods / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

To identify novel genes in castration-resistant prostate cancer (CRPC), we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus (GEO). R packages affy and limma were performed to identify differentially expressed genes (DEGs) between primary prostate cancer and CRPC. After that, we performed functional enrichment analysis including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway. In addition, protein-protein interaction (PPI) analysis was used to search for hub genes. Finally, to validate the significance of these genes, we performed survival analysis. As a result, we identified 53 upregulated genes and 58 downregulated genes that changed in at least two datasets. Functional enrichment analysis showed significant changes in the positive regulation of osteoblast differentiation pathway and aldosterone-regulated sodium reabsorption pathway. PPI network identified hub genes like cortactin-binding protein 2 (CTTNBP2), Rho family guanosine triphosphatase (GTPase) 3 (RND3), protein tyrosine phosphatase receptor-type R (PTPRR), Jagged1 (JAG1), and lumican (LUM). Based on PPI network analysis and functional enrichment analysis, we identified two genes (PTPRR and JAG1) as key genes. Further survival analysis indicated a relationship between high expression of the two genes and poor prognosis of prostate cancer. In conclusion, PTPRR and JAG1 are key genes in the CRPC, which may serve as promising biomarkers of diagnosis and prognosis of CRPC.

Comparison between analysis of HER2 gene and chromosome 17 in breast cancer by dual-probe chromogenic in situ hybridization and fluorescence in situ hybridization / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the application of dual-probe chromogenic in situ hybridization (dual-probe CISH) in analysis of HER2 gene status of breast cancer patients by comparison with fluorescence in situ hybridization (FISH). The potential impact of chromosome 17 polysomy in the determination of HER2 status was also studied.</p><p><b>METHODS</b>One hundred and forty-six cases of paraffin-embedded breast cancer tissues were retrieved. Analysis of HER2 gene and chromosome 17 copy numbers using CE-approved commercial kits of dual-probe FISH (for 146 cases) and dual-probe CISH (for 73 cases) were carried out. The results were interpreted according to ASCO/CAP, 2007 either HER2 gene copy number or the ratio of HER2/centromere 17 (CEN17).</p><p><b>RESULTS</b>Of the 73 cases analyzed by both FISH and dual-probe CISH, the concordance rates for negative and positive results was 91.7% (33/36) and 97.4% (37/38) respectively, while the overall concordance rate between the two methods was 95.9% (70/73). Of the 146 cases analyzed by FISH, 13 cases were interpreted as equivocal if only HER2 copies were counted, compared with 8 equivocal cases by calculating the ratio of HER2/CEN 17. Moreover, 3 cases (4.8%) of the 63 HER2-positive cases determined by HER2 copies turned out to be HER2-negative when determined by the ratio of HER2/CEN 17; while using dual-probe CISH, 1 (3.0%) of the 33 positive cases turned out to be negative. In addition, when using FISH, there were more chromosome 17 polysomy cases (63.5%, 40/63) in the HER2-positive subgroup than HER2-negative subgroup (37.3%, 28/75) (P = 0.002).</p><p><b>CONCLUSIONS</b>Dual-probe CISH can achieve similar results as compared to FISH, indicating that this technology is a reliable alternative to FISH in HER2 testing. The accuracy can further be improved when HER2 and chromosome 17 are simultaneously tested and counted.</p>

Clinicopathologic analysis of mixed epithelial and stromal tumor of kidney and adult cystic nephroma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunophenotype and differential diagnosis of mixed epithelial and stromal tumor of kidney (MEST) and adult cystic nephroma (CN).</p><p><b>METHODS</b>Five cases of MEST and 4 cases of CN were retrospectively analyzed. Immunohistochemical study was carried out and the literature was reviewed.</p><p><b>RESULTS</b>All of the five patients with MEST were females. Their median age was 45 years. For CN, there were 3 males and 1 female and their median age was 41 years. All patients presented with loin pain and hematuria. On gross examination, MEST was well-circumscribed but non-encapsulated. There was no evidence of haemorrhage or necrosis. Three of the cases were solid in nature. One was composed of a mixture of solid and cystic elements, while the remaining case showed a multicystic cut surface bridged by thick fibrous septa. On the other hand, CN were well-circumscribed and encapsulated. They were multiloculated cystic in nature. The cystic spaces were separated by thin septa and there was no significant solid or necrotic component. Histologically, MEST consisted of proliferation of cystically dilated glands admixed with spindly stromal cells with various cellularity and growth patterns. Both the glandular and stromal elements were well-differentiated with no cytologic atypia identified. The glandular structures in 2 of the cases were partially lined by endometrial or tubal epithelium. In contrast, the thin-walled cystic spaces in CN were lined by a single layer of epithelium.Immunohistochemical study showed that the epithelial cells were positive for pan-cytokeratin and epithelial membrane antigen. The spindle cells in MEST expressed vimentin (5/5), smooth muscle actin (3/5), desmin (4/5), CD10 (5/5), estrogen receptor (4/5) and progesterone receptor (4/5). They were negative for HMB45, CD34, CD117 and S-100 protein. On the other hand, the spindle cells in CN were variably positive for vimentin (4/4), smooth muscle actin (4/4), desmin (1/4), estrogen receptor (3/4) and progesterone receptor (1/4). They were negative for CD10, HMB45, CD34, CD117 and S-100 protein.</p><p><b>CONCLUSIONS</b>Both MEST and CN are uncommon renal neoplasm. Most of them run a benign clinical course. The stromal cells in MEST show smooth muscle or myofibroblastic differentiation. Areas demonstrating Müllerian features also existed in some cases. MEST and CN share overlapping histological and immunohistochemical features, and may represent spectrum of the same group of lesions.</p>

Inflammatory myofibroblastic tumor of bladder: a clinicopathologic study of five cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, diagnosis and differential diagnosis of inflammatory myofibroblastic tumor of the urinary bladder.</p><p><b>METHODS</b>Excisional specimens from 5 cases of vesical inflammatory myofibroblastic tumor were studied by light microscopy and immunohistochemistry (EnVision). The clinical data were also analyzed.</p><p><b>RESULTS</b>Among the 5 patients studied, 3 were males and 2 were females. The age of the patients ranged from 10 to 53 years (mean age = 35 years). The most common clinical presentation was micturition pain and hematuria. Three cases were located at the dome of the urinary bladder and the remaining 2 cases were found in the left lateral wall. Histologically, the tumor varied from myxoid to highly cellular. The tumor cells were spindle to stellate in shape, widely separated or showed a compact fascicular pattern. There were often associated with mixed inflammatory infiltrates and an irregular meshwork of small dilated vessels. Immunohistochemical study showed that the tumor cells expressed AE1/AE3 (5/5), vimentin (5/5), smooth muscle actin (5/5), calponin (5/5), caldesmon (3/5), desmin (4/5) and anaplastic lymphoma kinase protein (4/5). Follow-up data were available in 4 patients and none had local recurrence or died of this disease.</p><p><b>CONCLUSION</b>Inflammatory myofibroblastic tumour of urinary bladder is a rarely encountered but distinctive neoplasm with intermediate malignant potential.</p>

Expression of cyclin D1 and p27kip1 in renal cell carcinoma and its significance / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the role of cyclin D1 and p27(kip1) in the occurrence and development of conventional renal cell carcinoma(CRCC).</p><p><b>METHODS</b>RT-PCR and Western-blot were used to detect mRNA and protein contents of cyclin D1 and p27(kip1) in 25 CRCCs and 10 normal renal tissue distant to tumor. Immunohistochemistry was used to investigate the expression of cyclin D1 and p27(kip1) in pathological tissue sections of 76 CRCCs. The relationship between those index and clinicopathological parameters was analyzed statistically.</p><p><b>RESULT</b>In CRCC, the expression of cyclin D1 was higher than that of the control group. The higher cyclin D1 content was related to big tumor size (P<0.05); The expression of p27(kip1) was lower than that of the control group, and the lower p27(kip1) was related to higher nuclear grade and TNM stage (P<0.01). The 5-year cumulative survival rate of the p27(kip1) high expression group is longer than that of the low group (P<0.01).</p><p><b>CONCLUSION</b>The excessive expression of cyclin D1 and lower expression of p27(kip1) play an important role in the carcinogenesis of CRCC. The lower expression of p27(kip1) may affect the progression of the tumors. The detection of p27(kip1) may be as a reference marker in the prognosis of CRCC.</p>

Deep sarcoma of the penis: a report of 2 cases and review of the literature / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics, diagnosis, treatment and prognosis of deep sarcoma of the penis.</p><p><b>METHODS</b>The pathological and clinical data of 2 cases of deep sarcoma of the penis were analyzed retrospectively and the literature reviewed.</p><p><b>RESULTS</b>Both of the cases were treated by total penectomy. Epithelioid angiosarcoma of the penis was confirmed by postoperative pathology in one patient, who died of pulmonary metastasis in the eighth month after the operation; and epithelioid sarcoma of the penis was confirmed in the other, who died of brain metastasis in the second month after the operation.</p><p><b>CONCLUSION</b>Deep sarcoma of the penis is rare but can be diagnosed pathologically. Total penectomy is the main option for its treatment. Node dissection, with poor prognosis, is not recommended unless adenopathy is palpable.</p>

Distribution features of Gleason score and its relationship with clinical stages in 346 prostate cancer patients / 中华男科学杂志

<p><b>OBJECTIVE</b>To analyze the distribution features of Gleason score and evaluate the relationship between Gleason score and clinical stages in patients with prostate cancer.</p><p><b>METHODS</b>Surveys were made of the inpatients with prostate cancer diagnosed by pathology from January 1992 to June 2005 in our hospital. Gleason score and clinical stages were determined on the basis of pathological examination and clinical data of the prostate cancer patients. The patients were divided into three groups (1992-1999, 2000-2002 and 2003-2005). The Chi-square test was used to evaluate the distribution and differences of Gleason score among the three groups. Spearman rank correlation was applied to the evaluation of the relationship between Gleason score and clinical stages.</p><p><b>RESULTS</b>We found a statistically significant shift in the distribution of Gleason score (chi2 = 17.703, P < 0.01), and a slight increase in the mean Gleason score. The proportion of moderately differentiated tumor increased (chi2 = 10.736, P < 0.01). There was little change in the proportion of Gleason score 7, 8, 9 and 10 (chi2 = 4.038, P > 0.05). Gleason score had a significant positive correlation with clinical stages in the 346 cases of prostate cancer (r = 0.452, P < 0.01). Significant difference was observed between Gleason score 2-6 and 7 or 8-10 (chi2 = 8.786, P < 0.01, chi2 = 22.956, P < 0.01), but not between the latter 2 groups (chi2 = 0.787, P > 0.05) in prediction of organ-confined disease.</p><p><b>CONCLUSIONS</b>Gleason score 7 shows the similar value to Gleason score 8-10 in predicting the progression of the disease. Gleason score was significantly correlated with clinical stages, which suggests that Gleason score is also an important indicator for the prognosis of prostate cancer.</p>

Effects of Gardenia-aweto compound by different extraction method on antagonizing acute respiratory distress syndrome / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of Gardenia-Aweto compound (GAC) and two component on preventing acute respiratory distress syndrome (ARDS) by the rabbit model of ARDS induced by intravenous injection of oleic acid. To detect the efficiency component of GAC in preventing ARDS.</p><p><b>METHOD</b>GAC was divided into two compounts, ethanol-soluble components (ESC) and ethanol-deposition components (EDC), based on polarity. Forty-three new zealand rabbits were randomly divided into five groups, the blank control group, the model group, the GAC groups, the ESC group, and the EDC group. The ARDS model was induced by intravenous injection of oleic acid. Dynamic changes of arterial blood gas, lung index, albumin in bronchoalveolar lavage fluid (BALF) in different groups and lung histological changes were observed and compared.</p><p><b>RESULT</b>As compared with the blank group, in the model group, GAC group, ESC group, EDC group the arterial PO2 and oxygen saturation deprived continuously. While SO2 in GAC group at time points 30, 60, 90, 120 min (P < 0.05 or 0.01) and SO2 in ESC group at time points 30, 60, 90 min were higher than those in ARDS group. PO2 in ESC group at time points 30, 60 min (P < 0.05) were higher than those in ARDS group. The value of LI and W/D were higher in ARDS group than in sham group (P < 0.01), they were much lower in HD group than in ARDS group (P < 0.01). Concentration of BALF-albumin increased markedly in ARDS group and pre-treatment groups compared with sham group, but it was much lower in GAC group and ESC group, there was a significant difference between GAC group (P < 0.01), ESC group (P < 0.05) and ARDS group. The lung histological changes had been improved in GAC group and ESC group. But no significantly difference between above-mentioned parameters was found in comparison in the model group and in the EDC group.</p><p><b>CONCLUSION</b>Preventive administration of GAC or ESC an protect the damaged lung function in ARDS rabbits induced by oleic acid. The efficiency component of GAC in preventing ARDS is ESC. GAC antagonizing ARDS may relate to its anti-inflammatory, immuno-modulatory, anti-oxidant and antithrombotic effects.</p>

Study on independent factors on the prognosis of colorectal carcinoma: TNM stage, tumor budding, perineural invasion, peritumoral-lymphocytic infiltration and urine glucose / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the influence of clinical and pathological-morphological parameters on the prognosis of colorectal carcinoma.</p><p><b>METHODS</b>Univariate and multivariate Cox proportional hazard model were used to study the influence of clinical and pathological-morphological factors on the prognosis in 226 colorectal carcinoma cases.</p><p><b>RESULTS</b>Using univariate analysis, data showed that the factors significantly related to disease prognosis would include: the depth of direct spread, vessel invasion, perineural invasion, tumor budding, peritumoral-lymphocytic infiltration, Crohn-like reaction, number of positive lymph nodes, distant metastasis, TNM stage and urine glucose. Multivariate Cox proportional hazard model showed that six factors were identified to be associated with higher relative-risk (RR), including: older age, advanced TNM stage, more severe budding, perineural invasion, less peritumoral-lymphocytic infiltration and urine glucose.</p><p><b>CONCLUSION</b>Age, TNM stage, tumor budding, perineural invasive, peritumoral-lymphocytic infiltration and urine glucose were independent predictors to the prognosis of colorectal carcinoma.</p>

Prognostic factors influencing postoperative survival in patients with

<p><b>OBJECTIVE</b>To summarize the experience of surgical resection, and to analyze the prognostic factors that can influence the postoperative survival in patients with small hepatocellular carcinoma (small HCC) of </= 3 cm in diameter.</p><p><b>METHODS</b>The clinicopathologic data of 105 cases with small HCC after resection between 1986 and 2003 were analyzed, all of which had been followed up for more than half a year (median time, 33 months). Nine clinicopathologic factors including preoperative alpha-fetoprotein (AFP) level, liver cirrhosis, Child-Pugh score, tumor size (> 2 cm vs. </= 2 cm) and number (single vs. multiple), capsule formation, portal vein tumor thrombi (PVTT), Edmondson tumor grade and surgical method were analyzed through the way of Log-rank and Cox Regression tests.</p><p><b>RESULTS</b>Postoperatively, the cumulative survival rate of 1, 3 and 5-year were 86.5%, 70.3% and 55.2% respectively, and the disease-free survival rate of 1, 3 and 5-year were 78.0%, 58.9% and 45.6% respectively. One patient died from esophagogastric variceal hemorrhage in 2 weeks after re-operation. Up to the time of following up, 36 had intrahepatic recurrence or metastases postoperatively. Thirty-four patients died, of which, 4 died from variceal hemorrhage, 1 from liver failure, 1 died of pneumonia and 2 from distant metastases, while the others died from intrahepatic recurrences or metastases. Kaplan-Meier and multivariate Cox Regression tests indicated that poor Child-Pugh score, tumor more than 2 cm in diameter, PVTT and multiple lesions (including satellitic lesions) were adverse factors affecting postoperative survival. Multivariate Cox Regression tests indicated that tumor size, PVTT and multiple lesions were the factors affecting postoperative disease-free survival.</p><p><b>CONCLUSIONS</b>Limited hepatectomy with a margin no less than 1 cm is an appropriate surgical approach. Adverse preoperative Child-Pugh score and postoperative intrahepatic recurrences are main factors leading to the death of patients with small HCC.</p>

Carcinoma showing thymus-like differentiation of the thyroid: a study of 2 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To describe the pathologic features and differential diagnosis of carcinoma showing thymus-like differentiation (CASTLE) of thyroid.</p><p><b>METHODS</b>The clinical findings, morphologic features and immunohistochemistry (EnVision) of 2 cases of CASTLE were studied.</p><p><b>RESULTS</b>Macroscopically, the tumor appeared as a hard grayish-white and slightly lobulated mass. Histologic examination revealed well-circumscribed islands of tumor cells associated with desmoplastic stroma. The tumor cells were polygonal to spindle in shape and contained lightly eosinophilic cytoplasm, oval nuclei and small distinct nucleoli. The nuclear atypia was mild to moderate and the mitotic count measured 1 to 2 per 10 high-power fields. Immunohistochemical study showed that the tumor cells expressed CD5 and CD117.</p><p><b>CONCLUSIONS</b>CASTLE is a rare type of thyroid carcinoma with distinctive morphologic findings. It needs to be distinguished from undifferentiated thyroid carcinoma, squamous cell thyroid carcinoma, metastatic lymphoepithelioma-like carcinoma and follicular dendritic cell sarcoma. Immunohistochemical staining for CD5 and CD117 is helpful in confirming the diagnosis.</p>

Age and pathological features of 481 prostate cancer patients / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the age and pathological features of prostate cancer patients in recent years.</p><p><b>METHODS</b>An analysis was made of the age and pathological features of 481 cases of prostate cancer pathologically diagnosed from January 1998 to April 2004, 39 cases in 1998, 69 in 1999, 73 in 2000, 68 in 2001, 72 in 2002, 121 in 2003, and 39 in the first four months of 2004.</p><p><b>RESULTS</b>The patients ranged in age from 40 to 91 years, averaging 72, 95% between 55 and 84, and 84.2% over 65 years. Pathologically, 14 cases were well, 29 moderately, and 83 poorly differentiated according to the three-grade system (WHO, the Mostofi system), with 355 cases ungraded. Forty cases (8.3%) were microcarcinoma (< 1 cm), and 20 cases (4.2%) incidental carcinoma. Of the total number, 473 cases (98.1%) were pathologically diagnosed as adenocarcinoma, 1 endometrioid adenocarcinoma, 1 squamous cell carcinoma, 1 signet ring cell carcinoma, 1 adenosquamous cell carcinoma, 1 small cell carcinoma, 1 mucinous adenocarcinoma, 1 adenoid cystic carcinoma, and 1 transitional cell carcinoma.</p><p><b>CONCLUSION</b>Prostate cancer commonly develops in men over 65 years, and adenocarcinoma is the most common histological type. The disease has become a major malignant tumor to endanger elderly males.</p>

Effect of tea polyphenols on alcoholic liver injury / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To reproduce an experimental model of alcoholic liver disease in rats and to investigate the preventive and treatment effects of tea polyphenols on alcoholic liver disease.</p><p><b>METHODS</b>68 male Sprague-Dawley rats were randomly divided into 3 groups: alcohol group (gastrically infused with 56% of ethanol once a day with a dose of 7 g/kg body weight for 4, 12 and 24 weeks), tea polyphenols group (gastric infusion with alcohol same as in the alcohol group and with tea polyphenols at 0.25 g/kg bw) and control group (gastric infusion with normal saline). At the end of 4, 12 and 24 weeks, blood samples were collected and then the rats were sacrificed. Liver samples were obtained for routine histological examination and the degree of hepatic steatosis and alcoholic hepatitis were examined. Blood specimens were used for evaluation of alanine transaminase (ALT) and aspartate aminotransferase (AST).</p><p><b>RESULTS</b>(1) The levels of the two transaminases were elevated with the increase of the duration of ethanol feeding and the difference is significant. TP significantly mitigated the increase of ALT and AST activities induced by the alcohol. (2) Histological changes of the liver injury indicated that piecemeal or focal necrosis of hepatocytes was present in the centrilobular area. As fibrosis advanced, broader septa were formed with central-central and centra-portal bridging necrosis. In the TP infusion group, the severity of the pathological changes was significantly milder.</p><p><b>CONCLUSION</b>The results of this study revealed that TP mitigated the development of alcoholic liver disease, and TP may be a potential drug for treatment of alcoholic liver disease.</p>

Juxtaglomerular cell tumor of the kidney: a clinicopathologic analysis of five cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the morphologic characteristics and immunophenotype of juxtaglomerular cell tumor of the kidney (JGCT), with discussion on its diagnostic clues and possible histogenesis.</p><p><b>METHODS</b>The clinical, pathologic and immunohistochemical features of 5 cases of JGCT were evaluated. In addition, 5 cases of hemangiopericytoma and 5 cases of cutaneous glomus tumor were selected for comparative immunohistochemical analysis.</p><p><b>RESULTS</b>The JGCT cases came from 4 females and 1 male (mean age at diagnosis = 32 years). All of them manifested symptoms of systemic hypertension. Four of the patients received partial nephrectomy and the remaining patient was treated by radial nephrectomy. All of them were followed up for a period of 4 to 66 months (average = 27 months). There was no evidence of local recurrence or distant metastases. On gross examination, these JGCTs were well-circumscribed and situated in the renal cortex and measured 4.4 cm in greatest dimension on average. Histologically, the tumor was characterized by the following three features: (1) solid sheets of relatively uniform polygonal to round cells with lightly eosinophilic cytoplasm, sometimes containing PAS-positive intracytoplasmic granules; (2) absence of or very scanty mitotic figures; (3) interstitium rich in thin-walled capillaries, associated with focal hyaline change and hemangiopericytoma-like architectural pattern. Under electron microscopy, characteristic rhomboid-shaped renin granules were found in the cytoplasm. All JGCTs were immunoreactive for renin, CD34, actin, and calponin. In contrast, all glomus tumors were negative for renin and all hemangiopericytomas were negative for actin.</p><p><b>CONCLUSIONS</b>JGCT is a rare benign renal neoplasm typically found in young adults and manifests as systemic hypertension. The tumor cells may be originated from modified vascular smooth muscle cells. The identification of renin granules by electron microscopy and demonstration of the characteristic immunophenotype is the key to correct pathologic diagnosis.</p>