Expressions and prognostic significance of PTEN and PD-1 protein in patients with classical Hodgkin's lymphoma / 中华血液学杂志

Objective: To elucidate the expression levels of key immune biomarkers, phosphate and tension homology deleted on chromosome ten (PTEN) and programmed cell death protein1(PD-1),of different immune tolerance pathway in classic Hodgkin's lymphoma (CHL) to further determine their clinical role and prognostic significance. Methods: The clinical features and prognostic factors of 56 CHL patients, who were admitted to the TianJin Medical University Cancer Institute from February 2003 to August 2013, were retrospectively analyzed. PTEN and PD-1 protein expression levels were analyzed by immunohistochemistry, Epstein-Barr virus encoded RNA (EBER) was performed by in situ hybridization assay. Correlations between the expression of biomarkers and clinicopathologic parameters were examined and survival analyses were performed. Results: This cohort of 56 CHL patients included 34 males and 22 females with a median age of 25 years (ranged from 7 to 71 years). In a univariate analysis, age≥45, IPS score >2, EBER positive, high expression of PTEN protein conferred inferior 5-year OS and 5-year PFS; In a multivariate model, age≥45, IPS score >2, EBER positive, high expression of PTEN protein were identified as the independent adverse prognostic factors for CHL. Conclusions: This study suggested for the first time that PTEN was independent prognostic immune biomarkers in CHL, which provided the novel therapeutic strategy of immune therapy for CHL.

Clinical study of intelligent phacoemulsification for hard nucleus cataract extraction / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the efficiency and safety of torsional phacoemulsification with or without intelligent phacoemulsification ( IP ) software in hard nucleus cataract extraction. METHODS: Ninety two eyes with Ⅳ - Ⅴ grades cataracts were enrolled in this randomized prospective study. Operated eyes were divided into two groups -those operated without IP software ( non- IP group, n =43) and those operated using IP software (IP group, n =49 ). The two groups were compared in terms of ultrasound time (UST) and cumulative dissipated energy (CDE). Post- operative outcome measures included the corneal edema and best-corrected visual acuity (BCVA) at 1,7d and 3mo postoperatively, corneal endothelial cell density and percentage of hexagonal cell at 7d and 3mo postoperatively. RESULTS: UST was measured as 52. 51±9. 64s in non-IP Group and 48. 79±7. 13s in IP Group (P = 0. 030). CDE was 15. 78±3. 73% in non-IP Group and 14. 29±2. 77% in IP Group ( P = 0. 026). At the first postoperative day, the rate of BCVA>0. 1 in non-IP Group was 56%, and the rate in IP Group was 79% (P= 0. 066). Corneal edema in non-IP Group was 2. 98±0. 77 scores, and in IP Group it was 2. 61±0. 64 scores (P = 0. 021). At the postoperative 7 and 30d, the BCVA and corneal edema were no differences between two groups. At the postoperative 7d, corneal endothelial cell density in non- IP Group were 2497. 95 ±211. 48 / mm2 , less than 2586. 26±154. 71 / mm 2 in IP Group (P= 0. 029);percentage of hexagonal cell in IP group was 48. 33±8. 69%,higher than 44. 19±9. 48% of non-IP group(P= 0. 030).CONCLUSION: In hard nucleus cataract extraction, the IP software can combine the advantages of the two kinds of ultrasonic modes, which is more effective with lower ultrasound energy and less injury for the corneal endothclium, and is helpful for the recovery of vision at early stage after surgeries.

Protective effect of arctigenin in GK rats combined with hypertension macroangiopathy / 中国中药杂志

To study the protective effect of Arctigenin in goto-kakizaki (GK) rats combined with hypertension macroangiopathy. Six-week-old GK rats were divided randomly according to blood glucose level into four groups: the model group and low, middle and high dose arctigenin groups (12.5, 25, 50 mg x kg(-1)), with Wistar rats as the normal group. All of GK rats were given high-glucose and high-fat diet. After 16 weeks, GK rats were orally administrated with 10 mg x kg(-1) x d(-1) N-Ω-nitro-L-arginine methyl ester for eight weeks. During the modeling, all of arctigenin groups were orally administrated with different dose of arctigenin twice a day; The model group and the normal group were given solvents. At the beginning, mid-term and end of the experiment, blood glucose was measured. At the end of the experiment, efforts were made to detect blood pressure, collect abdominal aortic blood after anesthesia, fix thoracic aorta after bloodletting to make paraffin sections, observe morphological characteristics and detect the expression of VEGF by immunohistochemistry. According to the results, the blood glucose rose in all GK rats, with no significant difference between the drug group and the model group. At the end of the experiment, the blood pressure significantly increased in GK rats, indicating that Arctigenin could notably reduce the blood pressure in GK rats in a dose-dependent manner. The blood routine test showed increases in both the total white blood cell count and differential blood count, MPV and PDW, abnormal blood platelet parameters and decrease in PLT in GK rats, suggesting that Arctigenin could remarkably reduce the total white blood cell count and differential blood count, MPV and PDW. The thoracic aortic morphological observation revealed obvious endangium lesions in GK rats, demonstrating that Arctigenin could ameliorate the lesion extent. VEGF immumohistochemical staining showed a higher VEGF expression in the model group but lower expression in Arctigenin groups. In conclusion, Arctigenin had a protective effect on aorta in GK rats. Its mechanism may be related to blood pressure lowering, anti-inflammation, improvement in blood platelet function and reduction of VEGF expression.

Key nodes of a microRNA network associated with the integrated mesenchymal subtype of high-grade serous ovarian cancer / 癌症

Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition (EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentially present in mesenchymal cells. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas (TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This "paradox" can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating mRNA and microRNA (miRNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major miRNAs and 214 mRNAs. Among the 8 miRNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 miRNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer.

Resistance to apoptosis should not be taken as a hallmark of cancer / 癌症

In the research community, resistance to apoptosis is often considered a hallmark of cancer. However, pathologists who diagnose cancer via microscope often see the opposite. Indeed, increased apoptosis and mitosis are usually observed simultaneously in cancerous lesions. Studies have shown that increased apoptosis is associated with cancer aggressiveness and poor clinical outcome. Furthermore, overexpression of Bcl-2, an antiapoptotic protein, is linked with better survival of cancer patients. Conversely, Bax, CD95, Caspase-3, and other apoptosis-inducing proteins have been found to promote carcinogenesis. This notion of the role of apoptosis in cancer is not new; cancer cells were found to be short-lived 88 years ago. Given these observations, resistance to apoptosis should not be considered a hallmark of cancer.

Role of vasculogenic mimicry and endothelium-dependent vessel in metastasis of laryngeal cancer / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the contribution of vasculogenic mimicry (VM) and endothelium-dependent vessel (EDV) to invasion and metastasis of laryngeal squamous cell carcinoma (LSCC).</p><p><b>METHODS</b>A total of 203 cases with LSCC was reviewed and followed up. VM and EDV in LSCC tissues were assessed by double staining with anti-CD31 immunohistochemistry and periodic acid-schiff. Kruskal-Wallis test and one-way ANOVA were used to analyze the relationship between VM, EDV and clinical pathology parameters of LSCC. Kaplan-Meier analysis was used to evaluate overall survival (OS) of patients with LSCC.</p><p><b>RESULTS</b>VM related to pTNM stage, lymph node metastasis and pathology grade of LSCC, while EDV related to primary sites, pTNM stage, T stage and distant metastasis of LSCC. Univariate analysis showed VM (P = 0.014), pTNM stage (P = 0.009), T stage (P = 0.013), nodal status (P = 0.013), histopathology grade (P = 0.038), tumor size (P = 0.028), and radiotherapy (P < 0.0001) related to OS. VM (P = 0.011), primary sites (P = 0.049), tumor size (P = 0.001) and radiotherapy (P < 0.0001) related to disease free survival. Multivariate analysis indicated that VM was an adverse predictor for both OS and disease free survival.</p><p><b>CONCLUSIONS</b>Both VM and EDV existed in LSCC. VM contributed to progression of LSCC through promoting lymph node metastasis. VM is an independent predictor for the prognosis of LSCC.</p>

Vasculogenic mimicry is a key prognostic factor for laryngeal squamous cell carcinoma: a new pattern of blood supply / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recurrence and local lymph node metastasis affected the prognosis of patients with laryngeal cancer. The aim of this study was to analyze clinical and pathological significance of vasculogenic mimicry (VM) in laryngeal squamous cell carcinoma (LSCC) and evaluate its contribution to prognosis.</p><p><b>METHODS</b>Data of 168 cases of LSCC were reviewed retrospectively to reveal clinical pathology and prognostic significance of VM. CD31 and periodic acid-Schiff double staining was used to identify VM.</p><p><b>RESULTS</b>VM in LSCC contributed to lymph node metastasis (P = 0.003) and clinical progression. VM correlated to histopathology grade (P = 0.001) of LSCC. VM was an adverse prognostic factor for both disease-specific survival (P = 0.039) and metastasis-free survival (P = 0.042) by univariate survival analyses. And it was an independent prognostic factor for only disease-specific survival (P = 0.003) by multivariate survival analyses.</p><p><b>CONCLUSIONS</b>VM existed in LSCC. LSCC with VM has more potential to invasion and metastasis.</p>

Comparison of the effects of recombinant human endostatin and docetaxel on human umbilical vein endothelial cells in different growth states / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recombinant human endostatin (rh-endostatin, Endostar) has been proved to be an inhibitor of angiogenesis. Docetaxel has been also considered as a common chemotherapeutic agent with inhibition of angiogenesis of malignancies. However, their function has been seldom compared and a best synergism protocol is not determined. This study aimed to compare the effects of two drugs, investigate their combined impact on human umbilical vein endothelial cells (HUVECs), a molecular basis and find ideal protocols to inhibit endothelial cell proliferation.</p><p><b>METHODS</b>HUVECs on confluent growth or activated by vascular endothelial growth factor (VEGF) were treated by rh-endostatin or/and docetaxel at respective gradient concentration in following operations as cell proliferation determined by MTT assay, cell cycle distribution, apoptosis and markers of CD146, CD62E and CD105 detected by flow cytometery, the structure of the channel formed by HUVECs measured by tube formation count.</p><p><b>RESULTS</b>Rh-endostatin exhibited time dependent inhibition of proliferation while docetaxel showed both time and dose dependent inhibition. HUVECs accumulated in G(0)-G(1) with decreased numbers of cells in G(2) after a single treatment of rh-endostatin or that followed by docetaxel treatment. Cells accumulated in G(2) after both a single docetaxel and simultaneous administration. Both the number of cells in G(0)-G(1) and apoptotic cells were increased by docetaxel followed by rh-endostatin treatment. The number of non-apoptotic cells at G(0)-G(1) was increased by first administering rh-endostatin then docetaxel. Sequential treatment of docetaxel followed by rh-endostatin resulted in the greatest increase in apoptosis (34.7%) and the second highest apoptosis was seen with simultaneous administration (18.2%). Expression of CD146 and CD105 on confluent HUVECs was reduced at certain doses of rh-endostatin and/or docetaxel. However, rh-endostatin reduced CD105 without any apparent impact on either CD146 or CD62E expression, whereas these markers were down-regulated by docetaxel after pre-activation by VEGF. Rh-endostatin treatment maintained tube-like structures for a limited time. In contrast, docetaxel swiftly reduced tube formation. Simultaneous treatment, or docetaxel followed by rh-endostatin, exhibited a stronger inhibition on tube formation than either agent alone.</p><p><b>CONCLUSIONS</b>Both rh-endostatin and docetaxel can inhibit HUVEC proliferation while the high apoptotic rate after combined administration was probably owing to different sequent administration by docetaxel followed by rh-endostatin or simultaneous treatment. Both proliferation and adhesion molecules on HUVECs of confluent growth are down-regulated by the two drugs. The rh-endostatin decreased proliferation markers, but only slightly modified adhesion molecules, while both markers were down-regulated by docetaxel on HUVECs activated by VEGF. Rh-endostatin could maintain adhesion of HUVECs at first then induce cells apoptosis to damage tube formation. We hypothesize that it could lead to vascular normalization in short time. In contrast, docetaxel can suppress HUVEC proliferation, adhesion, and reduced tube formation swiftly due to its cytotoxicity. Combined treatments can induce a synergistic inhibition of tube formation.</p>

Significance of MUM-1/IRF4 protein expression in follicular lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of MUM-1/IRF4 and its significance in follicular lymphoma.</p><p><b>METHODS</b>Ninety-eight cases of follicular lymphoma were enrolled into the study. They were graded according to the 2008 WHO criteria. The expression of MUM-1/IRF4 protein and other markers (CD10, bcl-6, bcl-2 and Ki-67) was studied using tissue microarray and immunohistochemistry.</p><p><b>RESULTS</b>Amongst the 98 cases studied, there were 24 grade 1 cases, 30 grade 2 cases, 26 grade 3A cases and 18 were grade 3B cases. The rates of expression of MUM-1/IRF4, CD10, bcl-6, bcl-2 and Ki-67 (≥ 25%) were 39.8% (39/98), 62.2% (61/98), 80.6% (79/98), 87.8% (86/98) and 50.0% (49/98), respectively. MUM-1/IRF4 predominantly expressed in high-grade follicular lymphoma and showed a significantly positive correlation with lymphoma grade (r = 0.628, P = 0.000) and Ki-67 index (r = 0.473, P = 0.000). MUM-1/IRF4 expression had a significantly negative correlation with CD10 expression (r = -0.597, P = 0.000), but no correlation with bcl-6 and bcl-2 expression.</p><p><b>CONCLUSIONS</b>MUM-1/IRF4 expression is significantly higher in high-grade follicular lymphoma, indicating that these cases have a high proliferative activity, more aggressive behavior and poorer prognosis. MUM-1/IRF4, when strongly expressed, is another helpful marker for the diagnosis of high-grade follicular lymphoma.</p>

Relationship between SLP-2 expression and prognosis in laryngeal squamous cell carcinoma and mammary invasive carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of stomatin like protein-2 (SLP-2) at mRNA and protein levels in two kinds of malignant epithelial tumors, including laryngeal squamous cell carcinoma (LSCC) and invasive breast cancer, and to study the relations of SLP-2 expression and clinicopathologic parameters with the prognosis.</p><p><b>METHODS</b>RT-PCR and Western blot were used to detect the expression of SLP-2 mRNA and protein in LSCC and their normal counterparts (46 and 10 pair, respectively). Immunohistochemistry was carried on tissue array constructed from LSCC (104 cases) and breast cancer (263 cases), respectively. The association between SLP-2 expression and clinicopathologic parameters was analyzed.</p><p><b>RESULTS</b>LSCC showed a higher expression of SLP-2 than that of their normal counterparts (negative expression) at mRNA (83%, 38/46) and protein (7/10) level. Immunohistochemical analysis of LSCC showed that compared with negative expression in normal laryngeal epithelium (0/20), a higher SLP-2 expression was detected in LSCC (36/104, P=0.000) and associated with the advanced clinical stage (P<0.01) and lymph node metastasis (P=0.003). Immunohistochemical study of invasive breast cancer demonstrated that compared with negative expression in normal breast tissue (0/10), more than one half of the cases showed a high SLP-2 expression (52.5%, 138/263, P=0.000) in breast cancer, which correlated with the tumor size (P=0.020), lymph node metastasis (P<0.01), advanced clinical stage (P<0.01), distant metastasis (P=0.002) and HER2/neu protein expression (P=0.037). Survival analysis showed a shorter overall survival probability in patients with a high SLP-2 expression. It was considered that lymph node metastasis, positive HER2/neu expression, and high-level SLP-2 expression may act as the independent prognostic factors for those tumors.</p><p><b>CONCLUSIONS</b>A high expression level of SLP-2 may be associating with the development of invasion and metastasis in LSCC and breast cancer, and SLP-2 is also considered working as an independent factor indicating a poor prognosis clinically in breast cancer.</p>

Relationship between EGFR and K-ras mutations and clinicopathological characteristics and response to erlotinib treatment in 301 Chinese patients with non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate gene mutations of epidermal growth factor receptor (EGFR) and K-ras in Chinese patients with non-small cell lung cancer (NSCLC) and its clinicopathological significance, and to analyze the correlation between these mutations and tumor response to erlotinib treatment.</p><p><b>METHODS</b>Mutations of exons 18, 19, 20 and 21 of the EGFR and codons 12, 13 of the K-ras in 301 cases of NSCLC were detected by PCR-amplification and gene sequencing. The relationship between the mutations and clinicopathological characteristics of the 301 patients was analyzed.</p><p><b>RESULTS</b>EGFR mutations were present in 32.9% (99/301) of the samples: 3 mutation in exon 18, 59 in exon 19, 2 in exon 20, and 35 in exon 21. Mutations of K-ras were present in 4.7% (14/301) of the samples: 13 in codon 12 and 1 in codon 13. EGFR mutations were never found in tumors with K-ras mutations, suggesting a mutually exclusive relationship. EGFR mutations were more common in adenocarcinomas, non-smokers and females. Seven out of 10 erlotinib-treated patients with disease control carried EGFR mutation.</p><p><b>CONCLUSION</b>The frequency of EGFR mutation in Chinese NSCLC patients is higher than that in Westerners, but the frequency of K-ras mutation is quite opposite. Combined detection of EGFR gene and K-ras gene mutation may help clinicians to choose patients who may gain benefit from EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment, and to predict their response to erlotinib treatment and prognosis.</p>

Analysis of mitochondrial DNA D-loop region mutation and its significance in human oncocytoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the mutation in mitochondrial DNA displacement-loop (mtDNA D-loop) region in oncocytoma and its relationship with tumorigenesis and tumor development.</p><p><b>METHODS</b>The mtDNA D-Loop region of 20 thyroid or renal oncocytomas and the adjacent normal tissues were amplified by PCR, and then sequenced. Five human fetal renal tissues were collected as matched controls.</p><p><b>RESULTS</b>Among the 20 oncocytomas, 21 mutations which focused on hypervariable region I (HVI) were found in 7 tumor tissues and 1 normal tissue with the mutation rates of 35% and 5%, respectively. At the same time, 191 polymorphisms were found in the 20 cases.</p><p><b>CONCLUSION</b>mtDNA D-loop region, especially HV I, is the mutational hotspot of oncocytomas, which may be closely related with mtDNA duplicating rate and the function of mitochondria.</p>

Expression of SLP-2 protein in esophageal squamous cell carcinoma is associated with cancer invasion / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the expression of stomatin-like protein-2 (SLP-2) in esophageal squamous cell carcinoma (ESCC), and analyze the correlation between SLP-2 expression and clinicopathological features.</p><p><b>METHODS</b>The expression of SLP-2 protein in ESCC tissues (18 and 220 cases respectively) was detected by Western blot and IHC. The association between SLP-2 expression and clinicopathological features was analyzed.</p><p><b>RESULTS</b>Compared with normal epithelium, 13 cases of ESCC tissues showed a higher expression of SLP-2 on the protein level (72.2%, 13/18). IHC analysis on tissue microarray revealed that the expression rate of SLP-2 protein in ESCC was 54.1% and in normal esophageal mucosa was 3.6%, showing a significant difference (P < 0.001). SLP-2 high-level expression correlates with the extent of ESCC invasion (P = 0.033), but not with other clinicopathologic characteristics (P > 0.05).</p><p><b>CONCLUSION</b>SLP-2 as a novel cancer-related gene may play an important role in tumorigenesis of ESCC. The overexpression of SLP-2 may be closely associated with the invasion of esophageal cancer.</p>

Pilot study of differentiation of bone marrow derived mesenchymal stem cells into endothelial cells induced by B16 melanoma cells in vitro / 中华病理学杂志

<p><b>OBJECTIVE</b>Bone-marrow derived mesenchymal stem cells (BMSC) have the potential to differentiate into endothelial cells. The aim of the study was to investigate the induction process of BMSC by B16 melanoma cells in vitro and to analyze the role of VEGF-a in the process.</p><p><b>METHODS</b>A co-culture system containing BMSC and B16 melanoma cells based on transwell indirect model was established, and the induction process of BMSC by B16 melanoma cells was studied in vitro.</p><p><b>RESULTS</b>BMSC were isolated from the bone marrow of C57 mice. BMSC expressed CD105, CD90, CD73, CD44 and CD166, and acquired expressin of endothelial phenotype markers including VEGFR-1, VEGFR-2 and Factor VIII after co-culture with B16 melanoma cells for 48 hours. The expression level of VEGFR-2 would be double and Factor VIII threefold more by extending the co-culture time to 72 hours. In the co-culture system, B16 melanoma cells also up-regulated the expression of VEGF-a.</p><p><b>CONCLUSIONS</b>VEGF-a plays a significant role in the differentiation of BMSC into cells of endothelial phenotype, therefore, is important to tumor angiogenesis.</p>

Correlation of vasculogenic mimicry with clinicopathologic features and prognosis of ovarian carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the existence of vasculogenic mimicry (VM) in ovarian carcinoma and its correlationship with the clinicopathologic features and prognosis of the tumor.</p><p><b>METHODS</b>A total of 84 ovarian carcinoma cases were collected with complete clinical and prognostic data. CD31 immunohistochemistry and PAS special stain were used to investigate VM in the tumor tissue. Immunohistochemical staining of VEGF, MMP-2, MMP-9, E-cadherin, beta-catenin, and Vimentin were used to explore the pathogenesis of VM.</p><p><b>RESULTS</b>Totally 36 of 84 cases exhibited evidence of VM. FIGO classification, pathologic grades and histological types were significantly different between the VM and non-VM groups. Expression of VEGF, MMP-2, MMP-9, E-cadherin and beta-catenin were higher in the VM group than in the non-VM group. Kaplan-Meier survival curve analysis showed that cases of the VM group had a lower survival rate than that of the non-VM group (P = 0.04).</p><p><b>CONCLUSIONS</b>Vasculogenic mimicry exists in ovarian carcinoma. Ovarian carcinomas with a high grade malignancy have a high incidence of VM formation, a higher incidence of metastases and a lower survival rate. High expression of MMP-2 and MMP-9 may contribute to the formation of VM in the ovarian cancer.</p>

Relationship between the expression of hypoxia-inducible factor-1alpha and epidermal growth factor receptor and micro vessel density and their clinical significance / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>Analyze the relationship between the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and epidermal growth factor receptor (EGFR) and CD105 micro vessel density (MVD) and their value in evaluating biologic behavior and prognosis in laryngeal cancer.</p><p><b>METHODS</b>Ninety-one cases of laryngeal cancer were analyzed about their clinical and pathology data. In tumor tissue the expression of HIF-1alpha and EGFR was detected by immunohistochemistry and MVD was marked by CD105.</p><p><b>RESULTS</b>The expression of HIF-1alpha was correlated with size, TNM stage, T stage, lymph node metastasis and histological grade (all P<0.05). The expression of EGFR was correlated with TNM stage, lymph node metastasis, histological grade and relapse (all P<0.05). MVD was correlated with type, TNM stage, T stage, lymph node metastasis, metastasis and histological grade (all P<0.05). The expression of HIF-1alpha and EGFR was correlated with MVD (F value was 7.644 and 5.197 respectively, P value was 0.001 and 0.025 respectively). The correlation between the expression of HIF-1alpha and EGFR was significant statistically (r= 0.238, P=0.007). The survival rate of patients of 3 years and 5 years were 56.1% and 44.2% respectively. Survival analysis by Log Rank showed that prognosis of laryngeal cancer patients was correlated with type, TNM stage and the expression of both HIF-1alpha and EGFR. While Cox multiple factors analysis demonstrated that TNM stage and expression of EGFR were independent prognostic factor of laryngeal cancer (P value was 0.049 and 0.041 respectively, RR was 1.300 and 2.417 respectively).</p><p><b>CONCLUSIONS</b>HIF-1alpha and EGFR are key molecular event during development and progression of laryngeal cancer, which act in regulating tumor angiogenesis as well, and show intimate relationship with biological behavior and prognosis of laryngeal cancer.</p>

Diagnostic value of SYT-SSX fusion gene detection by fluorescence in-situ hybridization for synovial sarcoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To establish a method of SYT-SSX fusion gene detection by FISH and to explore its diagnostic value for synovial sarcoma.</p><p><b>METHODS</b>The presence of SYT-SSX fusion gene was determined by FISH using a tissue microarray containing 62 known synovial sarcomas, 60 non-synovial sarcomas and 133 equivocal synovial sarcomas. FISH results were compared with those of RT-PCR published previously.</p><p><b>RESULTS</b>Overall, 96.9% (247/255) of the cases were successfully analyzed by FISH. The sensitivity of FISH for known synovial sarcomas was 96.7% (58/60), and the specificity for the non-synovial sarcoma was 100% (59/59). Moreover, SYT-SSX gene fusion was detected in 78.1% (100/128) of the equivocal synovial sarcomas. The concordance rate between FISH and RT-PCR was 83.6% (102/122) in those equivocal synovial sarcomas, and overall 79.7% (106/133) of these cases were confirmed as synovial sarcomas either by RT-PCR or by FISH.</p><p><b>CONCLUSIONS</b>The sensitivity and specificity of FISH detection of SYT-SSX fusion gene are high. FISH and RT-PCR are complementary to each other in the confirmation of synovial sarcomas, particularly those questionable cases.</p>

Roles of immunohistochemistry and detection of SYT-SSX fusion gene in diagnosis of synovial sarcoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To assess the diagnostic values of immunohistochemistry and SYT-SSX fusion gene detection for synovial sarcoma.</p><p><b>METHODS</b>Based on clinical features, histological and immunohistochemical profiles, 195 cases of tumors were divided into three diagnostic categories: definitive synovial sarcoma, probable synovial sarcoma and possible synovial sarcoma. RT-PCR Detection of the SYT-SSX fusion gene was performed using paraffin embedded tissue samples. Comparison between RT-PCR and immunohistochemistry results was carried out and their diagnostic value was evaluated.</p><p><b>RESULTS</b>There were 62 (31.8%) definite synovial sarcomas, 49 (25.1%) probable synovial sarcomas and 84 cases (43.1%) possible synovial sarcomas. SYT-SSX fusion gene was detected in 140 (78.2%) cases overall, including 94.7% (54/57) definite synovial sarcomas, 86.0% (37/43) probable synovial sarcomas and 62.0% (49/79) possible synovial sarcomas. In tumors in the certain and probable synovial sarcoma categories, the positive rates of epithelial membrane antigen (EMA) were significantly higher in the SYT-SSX positive cases than SYT-SSX-negative cases (P = 0.022, P = 0.010, respectively). EMA was positively correlated with the presence of SYT-SSX (r(s) = 0.431, P = 0.001, r(s) = 0.463, P = 0.002, respectively). However, such a correlation was not seen in cytokeratin (CK), vimentin or S-100 protein immunostains (P > 0.05). In tumors of possible synovial sarcoma category, there were no significant differences of CK, EMA, vimentin or S-100 protein between SYT-SSX-positive and SYT-SSX-negative tumors.</p><p><b>CONCLUSIONS</b>SYT-SSX fusion gene detection is not needed when the conventional approaches are diagnostic. EMA positivity has a similar diagnostic value to that of SYT-SSX by RT-PCR for tumors in the probable synovial sarcoma category. However, detection of SYT-SSX is very important for diagnosis of the tumors in the category of possible synovial sarcoma.</p>

The influence of different microenvironments on melanoma invasiveness and microcirculation patterns / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the influence of different microenvironments on tumor microcirculation patterns and invasive capability.</p><p><b>METHODS</b>Melanoma B16 cells were injected into the peritoneal cavity and skeletal muscle of C57 mice synchronously. CK18 expression in melanoma was assessed to distinguish the malignant phenotype of tumors in the peritoneal cavity from that in the skeletal muscle. HIF-1alpha, MMP-2 and MMP-9 protein and mRNA expression were compared in the two microenvironments. Cells positive for each immunohistochemical stain and the vessels representative of each type of microcirculation pattern were evaluated in two microenvironments.</p><p><b>RESULTS</b>CK18 and HIF-1alpha expression in melanoma were significantly higher in the skeletal muscle than in the peritoneal cavity (t = 8.142, t = 3.645, P < 0.05). Compared with the peritoneal cavity, melanoma cells in the skeletal muscle overexpressed MMP-2 and MMP-9 (t = 4.916, t = 7.782, P < 0.05). Real time-PCR results also showed that MMP-2 and MMP-9 mRNA levels in melanoma were higher in the skeletal muscle than in the peritoneal cavity (t = 36.814, t = 26.025, P < 0.05). Vasculogenic mimicry channels and endothelium-dependent vessels were the major microcirculation patterns in the skeletal muscle and in the peritoneal cavity respectively.</p><p><b>CONCLUSIONS</b>Different microenvironments affect invasiveness and blood supply patterns of melanoma. Different microenvironment induced tumor cell secretion of more invasion-related proteins and affect invasiveness and blood supply patterns of melanoma.</p>

Effects of endostatin and doxycycline on microcirculation patterns in melanoma and their relevant molecular mechanisms / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effects of endostatin and doxycycline on microcirculation patterns in melanoma and their molecular mechanisms.</p><p><b>METHODS</b>To establish mouse B16 melanoma model by subcutaneous injection of B16 melanoma cell suspension. The mice were divided into 3 experimental groups and 1 control group. To treat the mice in the 3 experimental groups with endostatin, doxycycline, endostatin and doxycycline, respectively, and the control group without any treatment. The tumor volume was measured and recorded to make comparison of their growth rate. To assess the expression of MMP-2, MMP-9 and TIMP-2 by immunohistochemical staining. The three microcirculation patterns of endothelium-dependent vessels, mosaic vessels and vasculogenic mimicry were counted. The activity of MMP-2, MMP-9 between different groups was examined by gelatin zymography.</p><p><b>RESULTS</b>Tumor growth in the three experimental groups was statistically significantly slower than that in the control group. The expression of MMP-2, MMP-9 and TIMP-2 in each treated group was significantly different with that in the control group. The amount of three microcirculation patterns in three experimental groups was less than that of the control group, and the amount of MV and VM in each experimental group was significantly less than that in the control group. By gelatin zymography, the enzyme activity of MMP-9, actived-MMP-2 and MMP-2/proMMP-2 in ES, DOX and ES + DOX group was lower than that in the control group, but the enzyme activity of pro-MMP-2 among the four groups was not significantly different.</p><p><b>CONCLUSION</b>The combined use of doxycycline and endostatin in melanoma can inhibit the expression of MMPs, influencing the formation of different microcirculation patterns in melanoma.</p>