Biological effects of ubiquitin-specific peptidase 22 on thyroid papillary cancer cells and its mechanism of action.

BACKGROUND: In this study, ubiquitin-specific peptidase 22 (USP22) was detected in both thyroid papillary cancer-1 (TPC-1) and normal thyroid epithelial cell lines (HT-ori3), and its biological function was analyzed. METHOD: Cell culture, resuscitation, and passage, Western blot, and real-time polymerase chain reaction were used. RESULTS: The expression of USP22 was found to be significantly higher in TPC-1 cancer cells than in normal cells. After silencing of the USP22 gene in TPC-1 cells, the levels of USP22 gene and protein expression were significantly decreased. After 6 h with silencing of the USP22 gene, the migration rate was lower and the cells had become smaller than in the control group (P<0.05). At 24 h, the number of invasive cells was significantly lower than in the control group (P<0.05). A cell viability test showed that the differences between the groups increased on days 4 and 5 (P<0.05). The number of colony-forming cells had also decreased significantly after 10 days (P<0.05) in the USP22-siRNA1 group. Compared with the control group, the protein levels of USP22, cyclin D2, and Bmi-1 were significantly decreased (P<0.05). The decrease of USP22 was positively correlated with the decrease of Bmi-1 and cyclin D2. After silencing of the USP22 gene in normal HT-ori3 cells, the USP22 gene and protein expressions decreased significantly (P<0.05). A cell viability test showed that the difference had increased (P<0.01), and the number of cloned cells had significantly decreased than that in negative group (P<0.01). CONCLUSIONS: In conclusion, the USP22 gene plays a key role in the growth, proliferation, invasion, and migration of papillary thyroid cancer cells. USP22 possibly exerts its effect in TPC through the Bmi-1 and cyclin D2 pathways. USP22 also plays a crucial role in the growth of normal thyroid cells.

CUEDC2 Contributes to Cisplatin-Based Chemotherapy Resistance in Ovarian Serious Carcinoma by Regulating p38 MAPK Signaling.

Chemoresistance remains an obstacle to the successful treatment of ovarian carcinoma. CUE domain-containing 2 (CUEDC2) plays critical roles in tumor genesis and overexpresses in many solid cancers, including ovarian serous carcinoma. In previous study, we found that overexpression of CUEDC2 might be a promising biomarker to evaluate the progression and to predict likely relapse of serous ovarian carcinoma. In present study, we found that higher expression of CUEDC2 was associated with higher resistance to cisplatin. The overall survival (OS) and disease-free survival time (DFS) of patients with cisplatin resistant was shorter than that of those with cisplatin sensitive, respectively, and the cisplatin sensitivity was independent predictor of a shorter OS time and DFS time. Knockdown of CUEDC2 by small interfering RNA enhanced the cisplatin sensitivity of serous ovarian carcinoma cells in SKOV3 cell lines. Furthermore, the phosphorylation of p38 MAPK were obviously increased after CUEDC2 knockdown, while p38 MAPK signaling contributes to cell growth and cell apoptosis. Our data suggest that CUEDC2 takes part in cisplatin-based chemotherapy resistance by regulating p38 MAPK signaling. And CUEDC2 is a promising biomarker and therapeutic target of cisplatin resistance in ovarian serous carcinoma.

Transducer-like enhancer of split 1 (TLE1) as a novel biomarker for diagnosis of synovial sarcoma correlates with translocation t(X;18): a study of 155 cases in China.

Synovial sarcoma (SS) is a mesenchymal tumor of uncertain histogenesis which is defined by the translocation t(X;18). Transducer-like enhancer of split 1 (TLE1) as a new immunomarker for SS has offered an alternative to pathologists in distinguishing synovial sarcoma from other mesenchymal neoplasms, especially in limited molecular facilities. The main aim was to study the expression and diagnostic specificity and sensitivity of TLE1 in SS. We performed this immunohistochemical study on 155 SS (107 monophasic, 35 biphasic, and 10 poorly differentiated), 10 fibrosarcomas, 10 angiosarcomas, 10 epithelioid sarcomas, 10 Ewing sarcoma/PNETs and 8 malignant peripheral nerve sheath tumors (MPNST) using TLE1 immunomarker. Furthermore, in problematic cases (n=43), molecular confirmation was performed by fluorescent in situ hybridization (FISH) to detect the t(X;18) translocation. We correlated the TLE1 overexpression with the t(X;18) and other established biomarkers (CD117, CD56, cytokeratin AE1/AE3, EMA, CD99, BCL2, VIM, CD34, S100, Ki67, SMA). TLE1 expression was observed in 76.19% (112/147) of the SS, including 75.96% (79/104) of monophasic, 78.79% (26/33) of biphasic, and 70% (7/10) of poorly differentiated type. 65.99% (97/147) of SS cases showed a strong to moderate staining of TLE1. Other mesenchymal tumors showed very low or absent staining of TLE1 (P < 0.001). The overall sensitivity and specificity of TLE1 expression for the diagnosis of SS were 86.21% and 78.57%, respectively. Further molecular analysis showed that t(X;18) was clearly correlated with TLE1 expression (P=0.000). TLE1 is a specific and sensitive diagnostic immunomarker for SS and can be helpful to distinguish SS from other mesenchymal neoplasms.

Overexpression of Forkhead box Q1 correlates with poor prognosis in papillary thyroid carcinoma.

OBJECTIVE: Forkhead box Q1 (FOXQ1), a member of the forkhead transcription factor family, plays important parts in cell cycle, apoptosis, metabolism, immunology and tumour genesis. Its expression has been associated with poor clinical prognosis in various tumours. However, the clinical significance of FOXQ1 in papillary thyroid carcinoma (PTC) has not been fully studied. The purpose of this study was to investigate whether FOXQ1 is correlated with poor prognosis in PTC. DESIGN/METHODS: We performed a retrospective study of 136 PTCs. Immunohistochemistry (IHC) was used to examine the expression of FOXQ1 in 136 PTCs and 47 nodular goitre specimens. Rank-sum test, chi-square test, Kaplan-Meier survival analysis, univariate and multivariate Cox analyses were used to investigate the clinical and prognostic significance of FOXQ1 expression in PTC. RESULTS: The comparison of PTC specimens with nodular goitre with papillary hyperplasia specimens revealed an upregulation of FOXQ1 in PTC. Overexpression of FOXQ1 was observed in 63.24% of PTC and correlated with classic variant, tall variant, distant metastasis, AJCC stage and recurrence. FOXQ1-positive expression was associated with shorter disease-free survival: median disease-free survival of FOXQ1-positive patients was 23 months compared with 128 months for FOXQ1-negative patients (Log-rank χ2  = 12.31, P = 0.00045). Additional independent risk factors in this study were multifocality (recurrence-free survival [RFS]: hazard ratio [HR] = 2.391, P < 0.05), extrathyroidal extension (RFS: HR = 3.906, P < 0.05) and positive expression of FOXQ1 (RFS: HR = 6.385, P < 0.01). CONCLUSIONS: Our results indicated that FOXQ1 may be a useful additional biomarker to evaluate the progression of PTC and to predict likely relapse of disease.

[Complete atrioventricular septal defect: a clinicopathologic study of 35 cases].

OBJECTIVE: To investigate the autopsy characteristics, pathologic type, malfomation and genetic characteristics of complete atrioventricular septal defect (CAVSD). METHODS: Thirty five cases of CAVSD were collected from Maternal and Child Hospital of Haidian District during Jan.2003 to Jan.2015. Autoptic material, clinical history and chromosome examination were reviewed. RESULTS: Among 35 cases of CAVSD between 18-38 gestational weeks, there were 26 cases with CAVSD A (74.3%, 26/35), 1 case with CAVSD B (2.8%, 1/35) and 8 cases with CAVSD C (22.8%, 8/35). Only CAVSD malformation was seen in 4 cases (11.4%, 4/35). Multiple malformations were seen in 31 cases (88.6%, 31/35). Combined malformations most frequently occurred in cardiovascular, respiratory and locomotor system. Among 15 cases with chromosome examination, chromosome aberrations was found in 13 cases (13/15) and trisomy-21 was found in 11 cases (11/15). CONCLUSIONS: CAVSD is a rare disease and CAVSD A is the most common type. CAVSD is usually combined with other malformations and chromosome aberrations.

[Clinicopathologic study of 25 cases of placental chorioangioma].

OBJECTIVE: To investigate the clinicopathological characteristics, diagnostic criteria and differential diagnosis of placental chorioangioma. METHODS: Twenty-five cases of placental chorioangioma were analyzed for their clinical data, histomorphology and immumohisto chemical staining. Relevant literature was reviewed. RESULTS: The average age of the 25 patients was 29 years. Fourteen patients had full-term pregnancy, 10 had preterm labor, and 1 had intrauterine fetal death. Nineteen patients had pregnancy complications. The tumors presented as red or dusty pink nodules with clear borders. The tumor size ranged from 1 to 16 cm. Microscopically, the tumors possessed abundant capillaries or cavernous blood spaces lined by hyperplastic endothelial cells. These cells were positive for CD34 and Ki-67 index < 10%. CONCLUSIONS: Placental chorioangioma is a rare benign tumor of the placenta, and is associated with various pregnancy complications. Misdiagnosis of cell-rich type tumor should be avoided.

P16 and Ki-67 expression improves the diagnostic accuracy of cervical lesions but not predict persistent high risk human papillomavirus infection with CIN1.

OBJECTIVE: To determine the association between the expression of p16 and Ki-67 and cervical lesions, and to evaluate the role of p16 and Ki-67 as prognostic markers for persistent high risk human papillomavirus (hr-HPV) infection. METHODS: Totally 1,154 cases of cervical biopsies were enrolled, 331 cases with negative for dysplasia (NEG), 462 with cervical intraepithelial neoplasia 1 (CIN1), 176 with CIN2, 163 with CIN3 and 22 with cervical squamous cell carcinoma (SCC). Furthermore, 283 women with CIN1 were recruited into 12-month follow-up, and HPV specific gene detection by polymerase chain reaction was used to detect hr-HPV of cervical secretions at 6-month-interval for 12-month follow-up period. 40 women were infected with persistent hr-HPV, 182 with transient infection and 61 unfected with hr-HPV. The expression of p16 and Ki-67 were evaluated by immunohistochemical method. The immunostaining results of p16 and Ki-67 were classified into four categories: negative, 1+, 2+ and 3+. RESULTS: There was significant increase in the expression of p16 (P<0.001) and Ki-67 (P<0.001) from NEG to SCC. The expression of Ki-67 (P<0.001) but not p16 (P=0.254) significantly increased in CIN2, CIN3. Ratio of p16 (P=0.215) and Ki-67 (P=0.495) positivity were not correlated with persistent hr-HPV infection. CONCLUSION: P16 and Ki-67 can improve the diagnostic accuracy of cervical lesions but can not predict persistent hr-HPV infection with CIN1.

Overexpression of CUEDC2 Predicts Poor Prognosis in Ovarian Serous Carcinomas.

CUEDC2, a newly reported protein, plays critical roles in many biological processes, such as cell cycle, inflammation and tumorigenesis, however, its expression in ovarian serious carcinoma is still poorly understood. In this study, we performed an immunohistochemical study on 101 cases of ovarian serous carcinoma tissues to investigate whether CUEDC2 is a useful biomarker to evaluate the progression of ovarian serous carcinomas. The data showed that the overexpression of CUEDC2 was observed in 59.4% of ovarian serous carcinoma tissue samples and correlated with histopathological grade, patient age at diagnosis, FIGO stage and recurrence. To assess the clinical relevance of CUEDC2, we analyzed the survival follow-up information, the results showed that CUEDC2-positive expression was associated with a shorter disease-free survival time, the median disease-free survival time of CUEDC2-positive patients was 36.0 months compared with 53.9 months of CUEDC2-negative ones (Log-rank χ(2)=6.149, P=0.013). Collectively, our results suggested that CUEDC2 may be a promising biomarker to evaluate the progression of serous ovarian carcinoma and to predict likely relapse of ovarian serous carcinoma.

[Congenital pulmonary airway malformation of lung in fetus: a clinicopathological analysis].

OBJECTIVE: To study the etiology, pathogenesis, clinicopathologic characteristics, prognosis and treatment of congenital pulmonary airway malformation (CPAM). METHODS: Eighteen cases of CPAM were enrolled into the study. The clinical history, autopsy findings and immunohistochemical results were evaluated, with review of literature. The pathogenetic mechanism, pathologic features and differential diagnosis of CPAM were studied. RESULTS: Histologic examination showed that 2 cases were classified as Stocker type I, 12 cases as type II, and 4 cases as type III. The lesion was unilateral and involved single lobe in 13 cases. The remaining 5 cases had bilateral diseases. Of the 18 cases studied, 12 cases showed single organ involvement and 6 cases had malformations affecting multiple organs. The associated malformations included cardiac anomalies (4 cases), polycystic kidney with gastrointestinal atresia (1 case) and nuchal cystic hygroma with hydrothorax (1 case). CONCLUSIONS: CPAM is a rare pulmonary disorder. The etiology of this non-neoplastic condition is unknown. Imaging analysis is a valuable tool to suggest CPAM, while definite diagnosis requires pathologic examination. The overall prognosis is determined by the presence of associated malformations, fetal hydrops and pulmonary hypoplasia.

[Validation of HJ-1B thermal infrared channels onboard radiometric calibration based on spectral response differences].

Since HJ-1B was launched, 7 sets of blackbody data have been used to calculate onboard calibration coefficients, but the research work on the validation of coefficients is rare. According to the onboard calibration principle, calibration coefficients of HJ-1B thermal infrared channel on Sep 14th, 2009 were calculated with the half-width, moments and look-up table methods. MODIS was selected for the reference sensor, and algorithms of spectral match were improved between the HJ-1B thermal infrared channel and MODIS 31, 32 channels based on the spectral response divergence. The relationship of top of atmosphere (TOA) radiance between the remote sensors was calculated, based on which the surface leaving brightness temperature was calculated by Planck function to validate the brightness temperature calculated through the onboard calibration coefficients. The equivalent brightness temperature calculated by spectral response divergence method is 285.97 K, and the inversion brightness temperature calculated by half-width, moments and look-up table methods is 288.77, 274.52 and 285.97 K respectively. The difference between the inversion brightness temperature and the equivalent brightness temperature is 2.8, -11.46 and 0.02 K, respectively, which demonstrate that onboard calibration coefficients calculated by the look-up table method has better precision and feasibility.

[Clinicopathologic features of fetal nuchal cystic hygroma: report of 40 cases].

OBJECTIVE: To study the pathogenesis, pathologic features and prognosis of fetal nuchal cystic hygroma. METHODS: Forty autopsied cases of fetal nuchal cystic hygroma were collected during January 2003 to December 2012. The clinical history, pathologic changes and immunohistochemical (EnVision method) findings were reviewed, and the pathogenesis and pathologic characteristics were analyzed. RESULTS: Of the 40 cases, 16 (40.0%) showed single malformation and 24 (60.0%) were associated with multiple malformations in other organs and/or systems.Nineteen cases were septated and 21 were not. The associated malformations occurred in the respiratory system, skeletal system and urinary system.In the cases of combined malformations of umbilical cord, 3 were single umbilical artery malformations and 1 was torsion and stricture of umbilical cord.Four cases had chromosomal analysis, and all were trisomy-21. CONCLUSIONS: Fetal nuchal cystic hygroma is a rare disease. The etiology is unknown, but it is not neoplastic.Lymphangioma is divided into 3 types:capillary lymphangioma, cavernous lymphangioma and cystic hygroma according to their expansile growth pattern. The overall prognosis is determined by any co-existing chromosomal anomalies, associated malformations and the time of diagnosis of the cystic hygroma.

[Expression and clinicopathologic significance of CD44v6/CD24 in ovarian serous carcinomas].

OBJECTIVE: To study the expression and clinicopathologic significance of cancer stem cell markers CD44v6 and CD24 in ovarian serous carcinoma tissues. METHODS: One hundred and two cases of ovarian carcinoma diagnosed during the period from June, 2001 to December, 2010 were retrieved from archival files. The histology slides were reviewed and a two-tier system for grading of ovarian serous carcinoma was applied. The expression of CD44v6 and CD24 was detected by immunohistochemistry using EnVision method. The relationship between CD44v6/CD24 expression and various clinicopathologic parameters was analyzed. RESULTS: There were 46.1% (47/102) and 59.8% (61/102) cases expressing CD44v6 and CD24, respectively. Both CD44v6 and CD24 expression showed positive correlation with higher histopathologic grade (P = 0.003 and P < 0.05, respectively). CD24 expression also correlated with the presence of lymph node metastasis (P < 0.05). There was no statistically significant relationship between the expression of these two markers (χ(2) = 0.394, P = 0.530). The age of the patients, histopathologic grade, clinical stage and nodal status correlated with progression-free survival time (P < 0.05). CD44v6 expression and histopathologic grade correlated with the overall survival time (P < 0.05). Patient age was an independent poor prognostic factor by multivariate analysis. CONCLUSIONS: CD44v6 expression, age older than 50 years, high clinical stage and presence of lymph node metastasis are associated with poor prognosis in patients with ovarian serous carcinoma. The two-tier system for grading of ovarian serous carcinoma is useful in predicting survival; and high tumor grade represents an important poor prognostic indicator for ovarian serous carcinoma.

[Research on the atmospheric correction for ZY-3 MUX image].

The resolution of the ZY-3 MUX data is 5.8 meter, which is used to the subject classification. It is very difficult to use the dark target method for the atmosphere correction due to the lack of near infrared band in ZY-3 MUX data. The present paper uses the atmospheric correction coefficient look-up table (LUT) constructed by the radiation transmission model 6S based on the aerosol optical depth retrieved from the MODIS data for the atmospheric correction of ZY-3 image. To validate the results, the paper compares the surface spectral curves of the gypsum mine and Gobi and the NDVI values from the corrected and TOA reflectance, the relative error of the atmosphere corrected and the ground-based surface reflectance is less than 6%; the atmospheric correction increases the difference between vegetation NDVI and other features NDVI, highlights vegetation monitoring application ability.

[Value assessment of high-risk HPV test and TCT in the screening of cervical carcinoma].

OBJECTIVE: To estimate the status of coincidence of high-risk HPV (HR-HPV) test and thinprep cytology test(TCT) with biopsy histopathological diagnosis. And explore the diagnostic value in the cervical cancer and precancerous lesions by combination of these two methods. METHODS: Retrospective analysis cases with the positive cytological diagnosis. Acrodding to the principle of voluntariness and informed consent, 3197 cases were selected and further investigated by high-risk human papillomavirus testing and biopsy histopathological diagnosis. We had a comparative analysis to the coincidence of TCT, high-risk HPV-DNA test and biopsy histopathological diagnosis. RESULTS: Among 3197 cases, 58.6% cases with chronic inflammation, 26.1% cases with condyloma or CIN I, 14.1% cases with CIN II-III, and 1.2% cases with invasive cervical carcinoma. Compared with pathological biopsy, the coincident rate of the diagnosis of TCT cytology and histopathology were 21.2% (ASC-US), 28.6% (ASC-H), 39.6% (LSIL), 56.2% (HSIL) and 72.4% (cervical carcinoma), respectively. Among cases of positive TCT diagnosis, Compared HR-HPV test and histopathological diagnosis, infection rate of HR-HPV increases significantly with increasing pathological grade (chi2 = 292.354, P = 0.000 < 0.05). As the TCT diagnostic level increases, the positive rate of HR-HPV marked grows (chi2 = 144.113, P = 0.000 < 0.05). CONCLUSION: TCT can reduce the incidence of cancer effectively. But lower sensitivity in the low-grade cervical lesions may cause missed diagnosis. Combined TCT and HR-HPV test will improve the detection rate of cervical lesions; it is an ideal method to screening cervical cancer.

[Dandy-Walker complex: a clinicopathologic study of 9 cases].

OBJECTIVE: To investigate the etiology, pathogenesis, clinicopathologic characteristics, clinical prognosis and treatment of Dandy-Walker syndrome. METHODS: Nine cases of Dandy-Walker syndrome were included in the study. The autopsy findings and clinical history were evaluated along with review of the literature. The causes, pathogenetic mechanism, pathologic features and prognosis of Dandy-Walker syndrome were analyzed. RESULTS: Among 9 Dandy-Walker syndrome cases, six patients presented with variants of Dandy-Walker complex and 3 cases had classic Dandy-Walker malformation. In addition, 4 patients presented with combined lateral ventricle expansion and multiple malformations were seen in 7 cases. Combined umbilical cord abnormality was noted in 4 patients with variant of Dandy-Walker complex and combined placental abnormality was seen in one classic Dandy-Walker syndrome. CONCLUSIONS: Dandy-Walker syndrome is a rare disease. In addition to complex pathogenesis with possible genetic and environmental antigenic etiologies, placental and umbilical cord abnormality may be also related to its development.