Increased expression of macrophage migration inhibitory factor and DJ-1 contribute to cell invasion and metastasis of nasopharyngeal carcinoma.

BACKGROUND AND AIM: Both macrophage migration inhibitory factor (MIF) and DJ-1 protein have been shown to relate with cell invasion and metastasis in tumors. However, the role of DJ-1 in invasion and metastasis of nasopharyngeal carcinoma (NPC) and its relation to MIF expression in NPC are not fully understood. The aim of present study is to determine whether or not MIF and DJ-1 are correlated with tumor invasion and influence a worse outcome in NPC, as well as its related mechanism. METHODS: 125 cases of NPC and 45 normal tissues of nasopharynx were collected. The expression of MIF and DJ-1 in tissue microarray was evaluated by immunohistochemical staining. Correlation between immunostainings and clinicopathological parameters, as well as the follow-up data of patients, was analyzed statistically. The association of MIF and DJ-1 with cell invasion and migration in NPC cell line were evaluated by small interfering RNA (siRNA) transfection, invasion assay and Western blotting. RESULTS: MIF and DJ-1 staining was diffused and strong in tumor cells, whereas they were generally weaker and less common in normal lining epithelia of nasopharynx. High MIF expression in tumor cells (71.2%, 89/125 cases) were significantly associated with advanced clinical stage, lymph node metastasis, and worse prognosis of NPC patients. High expression of DJ-1 (75.2%, 94/125 cases) were closely correlated to lymph node metastasis and MIF high-expression. Only MIF high expression (P = 0.010) and lymph node metastasis (P = 0.004) emerged as strong independent prognostic factors for overall survival of NPC patients. In vitro, down-regulated expression of DJ-1 in NPC cell lines by siRNA was observed to reduce cell migration and invasion potential, however, exogenous MIF promoted cells invasion. CONCLUSIONS: The data provided evidence that increased expression of MIF and DJ-1 induced cell invasion and metastasis of NPC, supporting the idea that MIF and DJ-1 may play important roles as regulators in the progression of NPC.

Cognitive impairment induced by sevoflurane anesthesia is mediated by the cholinergic system after gastrointestinal surgery in older patients: A randomized, controlled trial.

Delayed neurocognitive recovery after surgery is associated with increased morbidity and mortality. However, its mechanism of action remains controversial and complex. A prospective, double-blind, randomized controlled trial was performed at the Affiliated Hospital of Zunyi Medical University. Older patients (aged 65 years and older) who underwent gastrointestinal surgery were randomly divided into sevoflurane-based or propofol-based anesthesia groups. The Mini-Mental State Examination was performed to evaluate cognitive function. Peripheral venous blood was collected to test the levels of choline acetyltransferase and acetylcholinesterase. A total of 75 patients were enrolled and 30 patients in each group completed the study. On Day 1 postoperation, patients in the sevoflurane group showed worse performance on the Mini-Mental State Examination than patients in the propofol group. Lower blood choline acetyltransferase concentrations and higher acetylcholinesterase concentrations were observed in patients who had sevoflurane anesthesia than in patients who had propofol anesthesia 1 day postoperative. At 3 days postoperation, patients with sevoflurane- or propofol-based general anesthesia did not differ regardless of Mini-Mental State Examination score or choline acetyltransferase and acetylcholinesterase levels. Sevoflurane-based anesthesia has short-term delayed neurocognitive recovery in older surgical patients, which may be related to central cholinergic system degeneration.

Unusual primary intracranial dural-based poorly differentiated synovial sarcoma with t(X; 18)(p11; q11).

Synovial sarcoma is a rare aggressive neoplasm occurring at any site of the body, mainly in young adults. It may also arise in the CNS but has seldom been reported. We report a case of unusual intracranial synovial sarcoma in a young male patient. Neuroimaging revealed a large gadolinium-enhancing mass was located at the right anterior cranial fossa and was associated with multiple cyst formation. The mass was dural-based and was observed to invade the right orbital apex and ethmoidal bulla. Histologically, the tumor was composed of uniform oval and round cells with scant cytoplasm and indistinct borders. The tumor cells were observed to form densely cellular sheets, but in some areas, the tumor showed hemangiopericytomatous vascular pattern consisting of tumor cells arranged around dilated, thin-walled blood vessels. By immunohistochemistry, vimentin, CD99 and Bcl-2 were diffusely positive in most cells, and a focally weak reactivity for S-100 protein was also observed. However, the tumor cells were negative for cytokeratin (AE1/AE3), CK7, CK8/18, CK19, epithelial membrane antigen, CD34, synaptophysin, GFAP, desmin, myogenin, and smooth muscle actin. Cytogenetic analysis using fluorescence in situ hybridization (FISH) demonstrated a translocation t(X;18)(p11;q11), an aberration specific for synovial sarcoma. A diagnosis of primary dural-based poorly differentiated synovial sarcoma was made. To our knowledge, this is the first report of a poorly differentiated variant of synovial sarcoma occurring in dura mater and confirmed by cytogenetic analysis. The present case indicates that appropriate immunohistochemical analysis, and in particular molecular analysis, are essential for accurately diagnosing small, round-cell neoplasms in unusual locations.

Bilateral cerebellar epithelioid hemangioblastoma with possible ependymal differentiation in a patient with von Hippel-Lindau disease.

There are controversies regarding the histogenesis of stromal cells of hemangioblastoma, and no hypothesis has conclusively been proven. We report a case of unusual hemangioblastoma in a middle-aged man with von Hippel-Lindau disease. Neuroimaging revealed multifocal gadolinium-enhancing masses were located within both sides of the cerebellar hemisphere. Histologically, only small areas showing the typical morphology of hemangioblastoma were recognized in masses. Most areas of masses were composed of cohesive epithelioid tumor cells with abundant cytoplasm and distinct boundaries. Epithelioid tumor cells were arranged around blood vessels, exhibiting perivascular anuclear zone structures like ependymoma. The epithelioid tumor cells were diffusely positive for vimentin, CD99, neuron-specific enolase, GFAP and focally positive for epithelial membrane antigen (EMA) and D2-40 in a dot-like pattern. Variable-sized lipid droplets and glycogen particles were noted in the cytoplasm of epithelioid tumor cells under an electron microscope. A diagnosis of epithelioid cellular hemangioblastoma with possible ependymal differentiation (WHO grade I) was made. To our knowledge, only a few cases of hemangioblastoma show epithelioid appearance or EMA immunoreactivity. The present case indicates that the stromal cells of hemangioblastoma might originate from primitive neuroectodermal cells, and they have the capacity to show a distinctive sign of glial or ependymal differentiation.

[Analysis of Epstein-Barr virus BamH I "f" variant in nodal metastasis of nasopharyngeal carcinoma].

OBJECTIVE: To investigate the Epstein-Barr virus (EBV) BamH I "f" variant in primary nasopharyngeal carcinoma (NPC) and its metastases in lymph nodes (LN). METHODS: In situ hybridization was used to detect EBV-encoded small RNA (EBER) expression in 21 paired paraffin-embedded tissue from primary NPC and their lymph node metastases and 22 primary NPC without lymph node metastasis. PCR and restriction fragment length polymorphism (RFLP) assay were used to detect EBV BamH I "f" variant in all cases of NPCs, lymph node metastases and 50 cases of chronic inflammation of nasopharynx from Canton. RESULTS: All cases of NPCs and their lymph node metastases showed EBER expression, indicating a high EBV-positive rate in Cantonese NPC patients. EBV BamH I "f" variant was found in 11 cases (52.4%, 11/21) of primary NPCs with LN metastasis, 12 cases (57.1%, 12/21) of the LN metastases, and 18 cases (81.8%, 18/22) of primary NPCs without LN metastasis. However, of the 50 cases of chronic inflammation of nasopharynx, only one case (2.1%, 1/47) demonstrated BamH I "f" variant. The frequency of BamH I "f" variant in NPC was therefore dramatically higher than that in chronic inflammation of nasopharynx. It is of note that atypical hyperplasia was observed in a few epithelial cells from the case of chronic inflammation of nasopharynx expressing BamH I "f" variant. CONCLUSIONS: The frequency of EBV BamH I "f" variant in NPC is significantly higher than that in chronic inflammation of nasopharynx. It is the first demonstration that the BamH I "f" variant is also present in the LN metastases of NPC. The frequency of BamH I "f" variant in metastatic NPC of the lymph node is almost equal to that of primary NPCs.

[Detection of cytokeratin 19 and thyroperoxidase expressions in the diagnosis of thyroid diseases].

OBJECTIVE: To investigate the value of detecting cytokeratin 19(CK19) and thyroperoxidase (TPO) expression in the diagnosis of thyroid diseases including thyroid carcinoma, multinodular goiter, adenoma and Hashimoto thyroiditis. METHODS: SP immunohistochemistry was used to detect the expressions of CK19 and TPO in paraffin-embedded thyroid tissue specimens obtained from 62 patients with thyroid carcinoma (30 with papillary carcinomas, 22 with follicular variant of papillary carcinomas, and 10 with follicular carcinomas) and 44 with benign thyroid diseases (including 22 with multinodular goiters, 14 with adenoma, and 8 with Hashimoto thyroiditis). RESULTS: CK19 expression was detected in 96.8% of the thyroid carcinomas and in 4.5% of benign thyroid diseases, demonstrating a significant difference in CK19 expression between the two thyroid diseases (P<0.01). TPO expression was found in 100% of benign thyroid disease and in 3.2% of thyroid carcinoma, showing also a significant difference between them (P<0.01). CONCLUSION: CK19 and TPO can be important molecular markers for diagnosing thyroid carcinoma.

[Relationship between liver mass and soluble intercellular adhesion molecule-1 in patients with liver cirrhosis].

OBJECTIVE: To investigate the relation of liver mass to, liver hymodynamics and soluble intercellular adhesion molecule-1 in patients with liver cirrhosis. METHODS: The liver mass was measured by liver biopsy, hepatic hemodynamics by ultrasonography, and the contents of hyalurionic acid (HA), human procollagen III (HPC III) and collagen type IV (C IV) by radioimmunoassay in 100 patients with liver cirrhosis in compensation stage and 30 normal control subjects. RESULTS: Greater liver mass was accompanied by more severe liver fibrosis and reduced liver blood flow. The contents of HA, HPC III and C IV were obvious higher in the patients than in the normal controls (P<0.05) and increased with the liver mass. The liver mass was positively related to serum liver fibrosis indices (r=0.5612, P<0.05). CONCLUSION: Liver mass in patients with liver cirrhosis is related to hepatic hemodynamics, indices for liver fibrosis and liver pathology.

Malignant transformation of nasal chondromesenchymal hamartoma in adult: a case report and review of the literature.

Nasal chondromesenchymal hamartoma (NCMH) is an extremely rare benign tumor arising in the sinonasal tract, predominantly involving infants and children. To date, only 27 cases are reported in the international literature and there have been no reported cases of malignant transformation. We present a 40-year-old female patient with nasal obstruction and bloody rhinorrhea. Computed tomography (CT) of the nose and paranasal sinuses confirmed a heterogeneous polypoid soft-tissue mass filling the nasal cavity and extending into the maxillary and ethmoid sinus. The patient underwent a complete radical resection. Histological and immunohistochemical analyses showed a portion of the mass was consistent with typical NCMH. However, some areas of mass exhibited cytological atypia, marked mitotic activity and foci of necrosis. The atypical mesenchymal spindle cells were immunoreactive for vimentin, CD99 and smooth muscle actin (SMA) diffusely. The cartilaginous cells were immunopositive for S-100 protein. Ki-67 index was high in atypical areas, accounting for 50%. A rapid mass recurrence was observed at the original site only 3 months after surgery. The final diagnosis of NCMH with malignant transformation was made. To our knowledge, this is the first report of malignant transformation occurring in an adult with NCMH. Although NCMH commonly develops in the neonate or young infants and exhibits benign histological appearance and favorable prognosis, there is a possibility of malignant transformation in adult patients. Thoroughly histological inspections are suggested to be necessary to accurately diagnose this tumor when it is encountered in adults.

Secondary cutaneous Epstein-Barr virus-associated diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma: a case report and review of literature.

Only a few cases of extranodal Epstein-Barr virus (EBV)-associated B-cell lymphomas arising from patients with angioimmunoblastic T-cell lymphoma (AITL) have been described. We report a case of AITL of which secondary cutaneous EBV-associated diffuse large B-cell lymphoma (DLBCL) developed after the initial diagnosis of AITL. A 65-year-old Chinese male patient was diagnosed as AITL based on typical histological and immunohistochemical characteristics in biopsy of the enlarged right inguinal lymph nodes. The patient initially received 6 cycles of chemotherapy with CHOP regimen (cyclophosphamide, vincristine, adriamycin, prednisone), but his symptoms did not disappear. Nineteen months after initial diagnosis of AITL, the patient was hospitalized again because of multiple plaques and nodules on the skin. The skin biopsy was performed, but this time the tumor was composed of large, polymorphous population of lymphocytes with CD20 and CD79a positive on immunohistochemical staining. The tumor cells were strong positive for EBER by in situ hybridization. The findings of skin biopsy were compatible with EBV-associated DLBCL. CHOP-R chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab) was then administered, resulting in partial response of the disease with pancytopenia and suppression of cellular immunity. To our knowledge, this is the first case of cutaneous EBV-associated DLBCL originated from AITL in Chinese pepole. We suggest the patients with AITL should perform lymph node and skin biopsies regularly in the course of the disease to detect the progression of secondary lymphomas.

Suppression of nasopharyngeal carcinoma cell by targeting ß-catenin signaling pathway.

AIM: To investigate the role of ß-catenin in pathogenesis of nasopharyngeal carcinoma (NPC). METHODS: Cellular proliferation, apoptosis, matrix penetration assay, and western blotting were employed to determine cell biological changes in NPC cell lines transfected with ß-catenin siRNA. Immunohistochemistry staining was used to detect ß-catenin and Ki-67 expression in NPC tissue. RESULTS: ß-Catenin was upregulated in NPC cell lines and tissues compared with chronic nasopharyngitis tissue. ß-Catenin knockdown dramatically inhibited cellular growth, migration and invasion, but induced apoptosis of NPC cells. Further study showed that downstream genes of ß-catenin signaling pathway including cyclin D1, c-Myc, MMP2 and MMP9 expression were suppressed in NPC cell lines transfected with ß-catenin siRNA. CONCLUSION: Targeting ß-catenin signaling pathway may be a noval strategy for NPC therapy.

[Correlation of Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) to fascin and phosphorylated Stat3 in nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Latent membrane protein 1 (LMP1) of Epstein-Barr (EB) virus is an important oncogene. Fascin is an actin cross-linking protein involved in cell migration and adhesion. Phosphorylated signal transducer and activator of transcription 3 (pStat3) is a member of STATs family, which is closely related to tumorigenesis. This study was to investigate expressions of LMP1, Fascin and pStat3 in nasopharyngeal carcinoma (NPC) tissues and lymph node metastases of NPC, thus to explore their correlations to the initiation and progression of NPC. METHODS: Expressions of EBV-encoded small RNA (EBER), LMP1, Fascin, pStat3, p53, Ki-67 and Bcl-2 were detected in 43 NPC tissues (21 with and 22 without lymph node metastases) and 21 corresponding lymph node metastases using in situ hybridization or immunohistochemistry (IHC). Data were statistically analyzed. Expressions of pStat3 and Fascin were measured in the NPC cell line CNE1 transfected with LMP1-expressing plasmid using Western blot. RESULTS: Positive EBER expression was detected in all 43 NPC tissues and 21 lymph node metastases in NPC. The expression rates of LMP1, Fascin, pStat3, p53, Ki-67, and Bcl-2 were 69.8% (30/43), 93.0% (40/43), 72.1% (31/43), 90.7% (39/43), 88.4% (38/43) and 88.4% (38/43)in 43 NPC tissues, respectively. LMP1 expression was positively correlated with the expression level of Fascin, pStat3, p53, Ki-67 and Bcl-2 in 43 NPC cases(P < 0.05). LMP1 was found in 10 out of 21 (46.7%) lymph node metastases in NPC. In addition, LMP1 expression dramatically increased pStat3 and Fascin in CNE1 cells. CONCLUSIONS: LMP1 is expressed in lymph node metastatases in NPC. The expression of LMP1 is positively correlated with Fascin, pStat3 and the proliferation index of tumor cells. Moreover, LMP1 up-regulates pStat3 and Fascin in NPC cells.

[Expression of angiogenesis-related factors in invasive breast cancer and its clinical significance].

OBJECTIVE: To investigate the relation between expression of angiogenesis-related factors, namely vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGFbeta(1)), and microvessel count (MVC) in invasive breast cancer and analyze its clinical implications. METHODS: VEGF, TGFbeta (1) and CD34 expressions in 62 surgical specimens of invasive breast cancer and 12 normal breast specimens were examined by immunohistochemistry and HE staining. MVC was calculated according to the quantification of positive CD34 expression. Clinicopathological characteristics of the patients including age, tumor size, histological type and auxiliary lymph node metastasis were recorded and compared with the results of MVC VEGF and TGFbeta1 expression and detection. RESULTS: MVC and of VEGF and expressions TGFbeta (1) in invasive breast cancer group (55.62-/+11.07, 51.61%, 56.45%, respectively) were greater than those in the normal control group (12.65-/+5.73, 16.67%, 16.67%, respectively, P<0.05). MVC and the positivity rates of VEGF and TGFbeta (1) expressions were 65.53-/+20.36, 68.75% and 78.13%, respectively, in invasive breast cancer patients with axillary lymph node metastasis, significantly higher than those without metastasis (P<0.05). MVC was correlated with VEGF and TGFbeta (1) expressions in that MVC was significantly higher in patients positive for VEGF and TGFbeta (1) (62.82-/+16.31 and 59.35-/+12.76) than in those negative for their expressions (51.16-/+12.53 and 50.80-/+15.62, P<0.05). Significant correlation was also found between VEGF and TGFbeta (1) expressions (P<0.05). CONCLUSION: The interaction between VEGF and TGFbeta (1) mediates angiogenesis, and MVC and VEGF and TGFbeta (1) expressions are correlated to lymph node metastasis, which may provide reference for prognostic evaluation of invasive breast cancer.

[Expressions of h-TERT, c-myc, PCNA and cell apoptosis in liver carcinogenesis].

OBJECTIVE: To investigate the expressions of human telomerase reverse transcriptase (h-TERT), c-myc, and proliferating cell nuclear antigen (PCNA) in chronic viral hepatitis (CVH), liver cirrhosis and primary hepatocellular carcinoma (HCC) and understand their possible role in liver carcinogenesis. METHODS: Totally 157 liver disease specimens were collected, including 56 CVH, 52 liver cirrhosis and 49 primary HCC specimens. In situ hybridization was performed on these specimens to examine the expressions of h-TRET and c-myc mRNA, and immunohistochemistry carried out for PCNA detection, with the cell apoptosis detected with in situ ending labeling. RESULTS: In the CVH, liver cirrhosis and primary HCC specimens, h-TERT expression was detected at the frequencies of 11/56 (19.6%), 43/52 (82.7%) and 44/47 (93.6%), c-myc expression at 7/56 (12.5%), 21/52 (40.4%) and 26/47 (55.3%), with apoptotic index of (27.3-/+4.7)%, (16.5-/+2.6)% and (8.7-/+1.3)% and PCNA expression rate of (17.1-/+2.9)%, (49.3-/+7.8)% and (62.5-/+9.1)%, respectively. Correlations among h-TERT, c-myc, and PCNA expressions and the apoptotic index were not found in the examined tissues (P>0.05). CONCLUSION: Liver carcinogenesis may involve increased h-TERT, c-myc, and PCNA expressions and suppressed cell apoptosis.