Clinicopathological features and risk factors of neuroendocrine tumors in 256 patients / 天津医药

Objective To investigate the epidemiology, clinical manifestations, diagnosis, treatment and prognosis of neuroendocrine tumors (NETs). Methods Medical records of 265 patients with neuroendocrine tumors diagnosed and treated in our hospital from January 2006 to August 2015 were collected and retrospectively reviewed in this study. The clinicopathological data including gender, age of onset, initial symptoms, primary site, pathological conditions, diagnosis, treatment, prognosis and follow up were analyzed. Results The gender ratio M/F of the 265 cases was 160:105 (1.5:1), with mean age of (55.8±2.7) years, and the high incidence was in age of 55-65 years. The tumors were located in the colon and rectum (127 cases, 47.9％), lung (59 cases, 22.3％), stomach (21 cases, 7.8％), appendix (15 cases, 5.7％), small intestine (especially in the duodenum and pancreas, 10 cases, 3.8％), mammary gland (11 cases, 4.2％), neck (10 cases, 3.8％) and unknown primary site (12 cases, 4.5％). Patients with different tumor sites showed different symptoms. Patients with colorectal tumors mainly manifested as changes in bowel habits, such as diarrhea, constipation and blood in stool. The main manifestation of patients with primary pulmonary symptoms was cough or bloody sputum. The patients with tumors at stomach, appendix or small intestine showed many discomfort, such as abdominal pain and abdominal distention. Among the 265 cases, 186 patients were diagnosed as phase G1 (70.2％), 54 patients were diagnosed as phase G2 (20.4％) and 25 patients were diagnosed as phase G3 (9.4％). Immunohistochemistry showed that synaptophysin (Syn) was positive in 228 cases (86.4％), chromaffin A (CgA) was positive in 102 cases (38.5％), and C56 was positive in 74 cases (27.9％). A total of 232 patients were treated with surgery (87.5％), 28 patients received radiotherapy or chemotherapy treatment (10.6％) and 5 patients were not treated. One hundred and ninety-eight patients were followed up at least 1 time, and the follow-up rate was 74.7％. The median follow-up time was 38 months. No tumor related death was found in patients with phase G1 during the follow-up, 6 cases of tumor associated death were found in patients with phase G2 and 19 cases of cancer related death were found in patients with phase G3. Metastasis was found in all 23 patients with tumor related death. The survival rate of patients with neuroendocrine tumor (G1+G2) was significantly higher than that of patients with neuroendocrine carcinoma (G3, Log rankχ2=13.774,P<0.01). Conclusion The males have a higher incidence rate of NETs than females. Patients with different tumor sites showed different symptoms. The most common primary sites of NETs are the digestive tract, especially in patients with colorectal cancer. The more late the pathological stage, the worse the prognosis.

Review of clinical investigation on recurrence of gastric cancer following curative resection / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To discuss the present status and progress of clinical research on recurrence of gastric cancer after surgery, including patterns, clinicopathologic factors, prognosis, detection, diagnosis, prevention, and treatment strategies.</p><p><b>DATA SOURCES</b>The data used in this review were mainly from PubMed articles published in English from 2000 to August 2011. The search terms were "gastric cancer" and "recurrence".</p><p><b>STUDY SELECTION</b>Articles were selected if they involved clinicopathologic factors, detection methods, and treatment strategies of recurrence of gastric cancer.</p><p><b>RESULTS</b>Peritoneal recurrence is the most common pattern in recurrence of gastric cancer. The main risk factors for recurrence of gastric cancer are tumor stage, including depth of tumor invasion and lymph node metastasis, and Borrmann classification. The prognosis of patients with recurrence is very poor, especially patients with peritoneal recurrence. Systemic chemotherapy is still the main treatment method for patients with recurrent cancer. If complete resection can be accomplished, some benefits may be obtained from surgery for recurrence. However, standard treatment for patients with recurrence has not yet been established.</p><p><b>CONCLUSIONS</b>Early detection and diagnosis of recurrence is quite crucial for treatment and prognosis. The optimal therapeutic strategy for recurrence should be based on a multidisciplinary assessment and the patient's individual state and should involve combined therapy.</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>

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>

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>

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>

A study on vasculogenic mimicry in hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore if vasculogenic mimicry (VM) exists in hepatocellular carcinoma (HCC) and to explain the clinical significance of VM.</p><p><b>METHODS</b>Ninety-nine HCC resection specimens with complete clinical and prognostic data were collected. Immunohistochemical staining of CD31 and CD105, hepatocyte and PAS staining of the histological preparations were conducted to explore if VM exists in those HCC.</p><p><b>RESULTS</b>12.12% (12 specimens) of the 99 specimens exhibited evidence of VM. One of 40 HCC specimens (2.5%) which belong to Edmondson pathologic grade I-II exhibited VM; 11 of 59 HCC specimens which belong to Edmondson pathologic grade III-VI (18.64%) exhibited VM, the low differentiated HCC (grade III-VI) exhibited more VM specimens than the high differentiated HCC (grade I-II) (chi2=4.416, P < 0.05). The biological behavior of VM was assessed and the stages of the cancers, using the TNM (tumor, node, metastases) classification criteria, were analyzed. These parameters of the VM and non-VM groups were compared. The mean TNM stage of the VM group was not more advanced than that of the non-VM group. The hematogenous metastases ( lung, bone, peritoneum et al) between the 2 groups were compared, and in the VM group the hematogenous metastasis rate was higher (chi2=8.873, P < 0.01). Kaplan-Meier actuarial survival curves were used to compare the VM group (n = 12) with the non-VM group (n = 87). Median survival time of the VM group was 9 months and that of the non-VM group was 31 months. The VM group had a lower survival rate than the non-VM group (P < 0.01).</p><p><b>CONCLUSION</b>VM exists in HCC, and the higher invasive HCCs exhibit more VM than the less invasive HCCs. The HCC patients in the VM group had a higher rate of hematogenous metastases, a lower survival rate, and a poorer prognosis.</p>

Study on the molecular mechanism of endostatin and doxycycline in suppressing melanoma growth / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the molecular mechanism of endostatin and doxycycline effect on melanoma growth.</p><p><b>METHODS</b>A B16 melanoma mice model was established by intracutaneous injection of B16 cell suspension. The mice were treated with endostatin, doxycycline, endostatin and doxycycline respectively, the control group received no treatment. A time course study of tumor volume was performed to observe the antitumor effect. The expression of matrix metalloproteinase (MMP-9), MMP-2, TIMP-2 were examined by immunohistochemistry staining.</p><p><b>RESULTS</b>Tumors in endostatin treatment group, doxycycline treatment group, endostatin and doxycycline treatment group grew slower than in the control group. The difference of the average tumor volume in the doxycycline group and control group, in the doxycycline with endostatin treatment group and control group were statistically different. The positive expression ratio of MMP-2, MMP-9, TIMP-2 in each treatment group were statistically different from their control groups (F = 12.79, F = 5.56, F = 4.64; P < 0.05).</p><p><b>CONCLUSION</b>Doxycycline and endostatin are able to inhibit the expression of MMPs and promote expression of TIMP, which ultimately inhibits the growth of B16 melonoma.</p>

Expression of FasL and apoptosis in pulmonary tissue of rats exposed to silica at different time / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the change of the expression of the FasL receptor and apoptosis in the pathology of silicosis of the rats exposed to silica and their roles.</p><p><b>METHODS</b>Ninety-six wistar rats were randomizedly divided into the control group and the experimental group. The silicotic animal model was established by the direct tracheal instillation of silica into rat lungs surgically. The control rats underwent directly tracheal instillation of saline into lungs surgically. Eight rats from each group were sacrificed at different days. The expression of FasL receptor in the tissue of the model rats was detected by tissuechip microarray and immunohistochemistry and the cell apoptosis induced by silica was determined by TdT-mediated dUTP nick end-labeling method. The integral optical density of positive cells were quantitatively analyzed using Image-Pro Plus Version 4.5 for windows.</p><p><b>RESULTS</b>The expression of FasL in the lung tissue of the model rats on the 7th, the 14th, the 21st, and the 28th day was significantly higher than that in the control group (P < 0.05), and peaked at the 14th day after exposure to silica. Apoptotic cells in the lung tissue of the model rats on the 1st, the 3rd, the 7th, the 14th, the 21st, and the 28th day were significantly more than those in the control group, and peaked at the 7th and the 14th day after exposure to silica.</p><p><b>CONCLUSION</b>Silica can lead to apoptosis in lung tissues. FasL is expressed in all kinds of cells in the pulmonary tissues of the rats exposed to silica and leads to apoptosis. From the 7th day to 14th day, inflammatory cells dominate in apoptotic cells.</p>

Expressions and significance of E-cadherin and beta-catenin in synovial sarcoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the expression and significance of E-cadherin (E-cad) and beta-catenin (beta-cat) in synovial sarcoma.</p><p><b>METHODS</b>Expression of E-cad and beta-cat in 72 cases of synovial sarcoma were detected by tissue microarray technique and immunohistochemistry. The relationships between E-cad and beta-cat expression and clinicopathological data and survival rate were analyzed.</p><p><b>RESULTS</b>(1) 95.1% of dots on the tissue microarrays were observable morphologically. The background was clear and the contrast was vivid after immunohistochemistry. (2) The expression of E-cad was reduced in 56 patients (77.8%) and that of beta-cat was reduced in 51 patients (70.8%). (3) In patients with synovial sarcoma of monophasic fibrous type, grade III, and in patients with recurrence or metastasis, CK-negative and EMA-negative the rates of reduced expression of E-cad and beta-cat were significantly higher than those with primary sarcoma of biphasic type, grade II, CK-positive and EMA positive (P < 0.05 for all). (4) The survival of synovial sarcoma patients with E-cad and beta-cat expressions preserved was significantly better than those with reduced expressions (P = 0.012, P = 0.047).</p><p><b>CONCLUSION</b>The expression of E-cad and beta-cat is correlated with cell differentiation. Reduced expression of E-cad and beta-cat may indicate a high potential of recurrence or metastasis and poor prognosis. Tissue microarray technique is applicable for retrospective studies of large sample size.</p>

Effect of niacin on nitric oxide synthase expression in rat lung exposed to silica / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the effects of niacin supplemented in diet on temporal expression of nitric oxide synthase in rat lung exposed to silica by tissue array technology.</p><p><b>METHODS</b>Wistar rats were randomly divided into three experimental groups: saline-treated group, silica-treated group, niacin-treated group. There are 48 animals in each group. Animal models were established by direct tracheal instillation of silica into the rat lungs. Plasma level of niacin was measured by high performance liquid chromatography (HPLC). The expression of iNOS protein in the paraffin-embedded lung sections was measured with streptavidin/peroxidase (SP) immunohistochemistry on tissue microarray and quantified by Image-Pro Plus.</p><p><b>RESULTS</b>Plasma level of niacin in niacin-treated group were significantly elevated by 5.946 4, 17.422 0, 21.398 0, 16.091 0, 4.414 3 and 7.130 5 mg/L at 1, 3, 7, 14, 21 and 28 days after instillation of silica, as compared to control and silica-treated groups. Seven days after instillation of silica, iNOS integrated optical density (IOD) of the lung, total NOS and iNOS activities in bronchial alveolar lavage fluid (BALF) supernatant in silica-treated group significantly elevated by 273 421, 2.61 kU/L and 1.89 kU/L, respectively, in the saline-treated group, with statistical significance. Niacin treatment could significantly decrease silica-elevated iNOS integrated optical density (IOD) of the lung, total NOS and iNOS activities in BALF supernatant by 248.292, 1.50 kU/L and 0.91 kU/L in the silica-treated group, respectively, with statistical significance.</p><p><b>CONCLUSIONS</b>It is suggested that treatment with niacin could effectively attenuate the over expression of nitric oxide synthase in the rat lung induced by silica particles in our study.</p>

The expression of lung nitric oxide synthase in rat exposed to silica / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the time-effect of silica on the expression of lung tissue nitric oxide synthase (NOS) in early inflammatory damage stage of silicotic rat.</p><p><b>METHODS</b>Animal models were established by direct tracheal instillation of silica into rat lungs. Total NOS and induced NOS (iNOS) activities in bronchoalveolar lavage fluid (BALF) were assayed. The expression of iNOS protein in paraffin-embedded lung sections with Streptavidin/peroxidase (SP) immunohistochemistry were measured by tissue microarray and Image-Pro Plus.</p><p><b>RESULTS</b>Most of the expression of iNOS was in the cytoplasm of macrophages and neutrophils. iNOS integrated optical density (IOD) of lung tissue increased 1.47 x 10(5) and 2.73 x 10(5) more respectively in silicatreated rats 3, 7 days after exposure than in control rats (P < 0.05), and decreased 1.11 x 10(5) more 28 days after exposure (P < 0.01). The activities of iNOS in BALF increased by 0.86, 1.89 and 0.92 U/ml respectively 3, 7, 14 days after exposure (P < 0.05 or P < 0.01). The activities of total NOS in BALF increased by 1.43, 2.05, 2.61 and 2.19 U/ml respectively 1, 3, 7, 14 days after exposure (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>After silica instillation, the iNOS-positive cells in rat lung tissue were mostly macrophages and neutrophils. There is a parabolic changing trend in the level of expression of lung iNOS during 1 - 28 day exposure to silica.</p>

Study on vasculogenic mimicry in malignant melanoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the mode of angiogenesis between highly invasive malignant melanoma and poorly invasive malignant melanoma by immunohistochemistry and periodic acid-Schiff stain (PAS) and to discuss whether the tumor cells in highly invasive malignant melanoma carry vasculogenic mimicry through self-metamorphosis, thus acquiring blood supply to sustain their growth.</p><p><b>METHODS</b>Thirty cases of highly invasive malignant melanoma and 30 cases of poorly invasive malignant melanoma were retrieved and reprocessed as tissue microarray for further investigations. The tissue microarray sections were then stained with CD34 and PAS; and the positivity rates were compared.</p><p><b>RESULTS</b>There was a significant difference between CD34 and PAS staining in highly invasive malignant melanoma (P < 0.01). The difference was not statistically significant in poorly invasive malignant melanoma (P > 0.05).</p><p><b>CONCLUSION</b>Vasculogenic mimicry exists in some cases of highly invasive malignant melanoma. It is possible that the tumor cells can acquire blood supply to sustain growth and metastasize via this mechanism.</p>

Correlation between the expression of collgen IV, VEGF and vasculogenic mimicry / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the relationship between collgen (Col) IV, VEGF secreted by the tumor cells and vasculogenic mimicry (VM).</p><p><b>METHODS</b>158 bi-phase differential malignant tumor specimens were alloted and made into tissue microarray. These tissue microarray sections were stained with CD31, periodic acid-Schiff (PAS) and Col IV. Subsequently, distributive trait of Col IV and the difference of VEGF expression were analyzed.</p><p><b>RESULTS</b>The basement membrane of VM was PAS and Col IV positive. The expression of VEGF in bi-phase differential malignant tumor with VM was less than that in those without VM. The difference of VEGF expression in malignant melanoma and alveolar rhabdomyosarcoma was significant (P < 0.05).</p><p><b>CONCLUSION</b>Collgen IV and periodic acid-Schiff positive material take part in constructing the basement membrane of vasculogenic mimicry. The difference of the VEGF expression proves that vasculogenic mimicry can sustain the tumor blood supply.</p>