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This study was designed to describe the clinicopathological characteristics of cervical squamous cell carcinoma (SCC) intra epithelial spreading to the upper genital tract. A total of fifteen patients were enrolled, including eleven patients which were cervical SCC spreading to the endometrium, four patients whose squamous cell carcinoma intra epithelial spread along the uterine cavity to the adnexa. Clinical information and pathological data were collected. Human high risk HPV was detected by mRNA in situ hybridization. The average age was 55.07 years old. Twelve of the fifteen patients were post menopause women. The intra epithelial spread pattern can be seen in thirteen patients. Five of the fourteen patients received a uterine apoxesis, the other pre operative condition including chemotherapy, papillary thyroid carcinoma, thyroid hypofunction, and immune deficiency. HPV was positive in all the patients’ specimen, and the infection status of cervical lesions, endometrial lesions, and adnexal lesions were same. For the peculiar case twelve, the cervical CIS lesion intra epithelial spread along the mucosa of uterine cavity and fallopian tube, and invasive SCC can be identified in the uterine corpus, fallopian tubes and ovaries. Intra epithelial spread pattern is an indolent spreading pathway of the cervical SCC, it can involve the upper uterine tract even when the cervical lesion in at a very early stage, such as CIS. The deepest invasion site may not be the primary site. The intra epithelial spread may have relationship with pre operative disposal. High risk HPV detection can help to confirm the cervical origination.

Objective Recurrent hydatidiform moles are reportedly biparental complete moles and related to mutated NLRP7 and KHDC3L. This study was designed to identify mutations of gene NLRP7 and KHDC3L in biparental complete moles. Methods In this study, we have screened NLRP7 and KHDC3L mutations in five patients with recurrent moles and five with sporadic moles. Molar tissues and blood samples were collected from patients and their partners. Genotypes of the molar tissues were determined based on short tandem repeat polymorphism. The coding exons of NLRP7 and KHDC3L were sequenced. Results Two patients with recurrent moles had biparental complete moles, while all other patients had androgenetic complete moles. Three non-synonymous variants in NLRP7 (c.955 G>A, c.1280 T>C and c.1441 G>A) and one in KHDC3L (c.602 C>G) were identified in patients with recurrent moles. NLRP7 c.1441 G>A and c.1280 T>C were mutations found in the Chinese population, while c.1441 G>A was only detected in patients with biparental complete moles in this study. Conclusions Genotyping can be used to differentiate biparental complete moles from androgenetic moles and to predict the risk of recurrent moles in future pregnancies. NLRP7 c.1441 G>A may associate with biparental complete moles. Biparental complete moles exhibit genetic heterogeneity.

Background: Primary malignant tumors of the pericardium are rare, and most primary malignant pericardium tumors are mesotheliomas. Primary pericardial angiosarcoma is extremely rare, and it is associated with a poor prognosis. Case presentation: We report of a 47-year-old woman who complained of activity-related chest tightness and shortness of breath. Computed tomography, magnetic resonance imaging, and transesophageal echocardiography revealed an enlarged pericardium with hematic and solid components. An exploratory pericardiotomy was performed, and the results of the histological examination were suggestive of spindle cell hemangioendothelioma. She survived for 9 months after surgery without chemotherapy and radiotherapy, and she had a relatively good quality of life. Conclusion: Primary pericardial angiosarcoma is difficult to diagnose, and it has a poor prognosis. Pericardiotomy, radiation therapy, and chemotherapy were associated with a prolongation of survival.

It has long been regarded that pancreatic cancer (PC) is a life-threatening malignant tumor. Thus, much attention has been paid for factors, especially relative molecules, predictive for prognosis of PC. However, c-fos expression in PC was less investigated. In addition, its association with clinicopathologic variables and prognosis remains unknown. In the present study, expression of c-fos was detected by tissue microarray-based immunohistochemical staining in cancer and adjacent tissues from 333 patients with PC. The staining results were correlated with clinicopathologic parameters and overall survival. Furthermore, prognostic significance of c-fos in subsets of PC was also evaluated. It was shown that low expression of c-fos was more often in cancer than in adjacent tissues of PC (P

Angiomatoid fibrous histiocytoma (AFH) is a rare, low-grade malignant soft-tissue tumor most commonly occurring in the extremities of children and young adults and has a low potential of local recurrence and metastasis. Here, we present a case of recurrent subcutaneous perianal AFH. After an initial diagnosis as a sebaceous cyst, we were able to use immunohistochemical findings to correctly identify the mass as an AFH. The patient was effectively treated after 3 surgical resections. This case emphasizes the need to correctly diagnose soft-tissue tumors using a variety of diagnostic modalities to ensure that the patient receives proper treatment.

Purpose: Studies have shown that mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain are associated with response of lung cancer to gefitinib (Iressa, AstraZeneca Corp., Shanghai, China). A higher incidence of EGFR mutation was observed in non–small cell lung cancer (NSCLC) patients of Japanese origin compared with those of American origin. However, no data about such mutations in Chinese patients with NSCLC could be obtained. Methods: Primary NSCLC tissues were obtained for analysis of mutations in exons 18 to 21 of EGFR from a total of 76 patients, of whom 54 did not receive gefitinib therapy and 22 did. PCR products were sequenced directly and mutations were confirmed by an independent PCR and sequence analysis. All types of mutation were cloned and sequenced. Results: A total of 10 types of mutation were found in the series of patients, including two different silent mutations in exon 20 from 11 patients. More than half of the silent mutations (6 of 11) in exon 20 coexisted with other mutations. Mutations were more frequent in adenocarcinoma (17 of 35; 48.6%) compared with squamous carcinoma (1 of 19; 5.3%) among untreated patients. Similar mutations were observed in all seven gefitinib-treated patients with partial response, and no mutations were detected in all eight patients with progressive disease (P < 0.001), except two silent mutations. Three mutations were observed in seven patients with stable disease. Conclusions: Mutations in the epidermal growth factor receptor tyrosine kinase domain in lung adenocarcinomas from Chinese patients were more frequent than reported previously in lung adenocarcinomas from American patients. Such mutations were well correlated with tumor response to gefitinib.

Background Recent studies have shown the clinical significance of epidermal growth factor-like domain 7 (EGFL7) in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer (PC) remains unclear. The present study was undertaken to investigate the role of EGFL7 in the prognosis of PC. Methods The expression of EGFL7 in nine PC cell lines was first determined by Western blotting analysis. Tissue microarray-based immunohistochemical staining was performed in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 83 patients with PC. Finally, correlations between EGFL7 expression and clinicopathological variables as well as overall survival were evaluated. Results EGFL7 was widely expressed in all PC cell lines tested. EGFL7 expression in tumor tissues was significantly higher than that in non-tumor tissues ( P =0.040). In addition, univariate analysis revealed that high EGFL7 expression in tumor tissues was significantly associated with poor overall survival, accompanied by several conventional clinicopathological variables, such as gender, histological grade and lymph node metastasis. In a multivariate Cox regression test, EGFL7 expression was identified as an independent marker for long-term outcome of PC. Conclusion Our data showed that EGFL7 is extensively expressed in PC and that EGFL7 is associated with poor prognosis.

To explore the significance of succinate dehydrogenase B (SDHB) mutation and EPAS1 overexpression in Zuckerkandl paragangliomas (PGL) and examine their correlations with malignant infiltration and metastasis.From March 2008 to July 2011, the clinical profiles of 16 Zuckerkandl PGL patients were analyzed retrospectively. For increased diagnostic specificity, a complex immunohistochemical panel of tissue microarray was performed for SDHB, EPAS1 and MIB-1. Positive expression identified as a granular cytoplasmic staining. Greater than or equal to 50% as strongly positive (+++), 1% to 10% as weakly positive (+).Tissue microarray immunohistochemical staining showed SDHB immunoreactivity in the cytoplasm, whereas EPAS1 and MIB-1 in the nuclear of tumor cells. Positive expression of EPAS1 in which 13 cases of Zuckerkandl PGL. And high expression strongly associated with malignancy. SDHB mutation of 7 cases are all EPAS1 positive staining. Non-gene mutation 9 cases tumor specimens, 6 cases were EPAS1 positive expression (P0.05). CgA positive expression in 11 cases benign Zuckerkandl PGL, strongly positive in 4 malignant cases (4/4). MIB-1 below 1% in 12 cases of benign Zuckerkandl PGL. And in 4 malignant cases, MIB-1 was about 3%. Malignant neoplasms had significantly higher EPAS1, CgA and MIB-1 expression compared to benign counterparts (P0.05).The SDHB mutation causes the EPAS1 over expression in PGL and correlation with higher positive expression of CgA and MIB-1. It may be one of the mechanisms of malignant invasiveness and metastasis in PGL.

The biochemical response to ursodeoxycholic acid (UDCA) in primary biliary cirrhosis is a strong predictor of long-term outcome and thus facilitates the rapid identification of patients needing new therapeutic approaches. Numerous criteria for predicting outcome of treatment have been studied based on biochemical response to UDCA at 1 year. We sought to determine whether an earlier biochemical response at 3 or 6 months could as efficiently identify patients at risk of poor outcome, as defined by liver-related death, liver transplantation, and complications of cirrhosis. We analyzed the prospectively collected data of 187 patients with a median follow-up of 5.8 years (range, 1.3-14 years). The survival rates without adverse outcome at 5 years and 10 years were 86% and 63%. Under UDCA therapy, laboratory liver parameters experienced the most prominent improvement in the first 3 months (P < 0.0001) and then stayed relatively stable for the following months. The Paris, Barcelona, Toronto, and Ehime definitions, but not the Rotterdam definition, applied at 3, 6, and 12 months significantly discriminated the patients in terms of long-term outcome. Compared with biochemical responses evaluated after 1 year of UDCA therapy, biochemical responses at the third month demonstrated higher positive predictive value (PPV) but lower negative predictive value (NPV) and increased negative likelihood ratio (NLR) by all definitions; biochemical responses at the sixth month showed higher or the same PPV and NPV and lower NLR by all definitions. Conclusion: For the previously published criteria, biochemical responses at the sixth month can be used in place of those evaluated after 1 year of UDCA therapy. Our findings justify a more rapid identification of patients who need new therapeutic approaches. (HEPATOLOGY 2013)

Peritoneal tuberculosis and primary peritoneal carcinoma can both present as an abdominal mass and ascites with elevated serum CA125. The purpose of our study was to evaluate the clinical features of peritoneal tuberculosis, compare them with features of primary peritoneal carcinoma, and establish definitive diagnostic procedures.We conducted a retrospective study in patients with peritoneal tuberculosis from January 1995 to October 2010 at Peking Union Medical College Hospital. During this time, the data of 38 patients with primary peritoneal carcinoma were reviewed.The median age was 34 years (range, 19 - 80 years). The most common symptoms were abdominal distension (16/30, 53.3%) and an abdominal mass (12/30, 40.0%). The serum CA125 level was elevated in 25 patients (83.3%). The median level of cancer antigen CA125 was 392.5 U/ml (range, 0.6 - 850.0 U/ml). Abdominal ultrasound revealed a pelvic mass in 25 patients and ascites in 20 patients. Diagnostic laparoscopy was performed in 15 patients (50.0%) and exploratory laparotomy was performed in 12 patients (40.0%), and 3 patients (10.0%) who underwent laparoscopy converted to laparotomy because of severe adhesions. The intraoperative findings were adhesions, multiple white tubercles, and ascites. Frozen tissue sections were obtained in 17 patients, and 14 of whom showed chronic granulomatous reactions. Final pathological examinations confirmed the diagnosis.Peritoneal tuberculosis should be considered as a differential diagnosis, especially for young women with an abdominal mass, ascites, and elevated serum CA125 levels. Laparoscopy is a useful diagnostic method for peritoneal tuberculosis, and intraoperative frozen sections are recommended when the diagnosis is in doubt.

Background Danon disease is an X-linked dominant disorder; concentric left ventricular hypertrophy (LVH) is one of its manifestations. In this study, we investigated the prevalence of Danon disease in patients with concentric LVH who underwent endomyocardial biopsy (EMB). Methods and results A total of 50 patients with concentric LVH underwent EMB from January 2008 to December 2010. Cardiac amyloidosis was diagnosed in 14 patients; genetic analysis of lysosome-associated membrane protein 2 (LAMP2) was done in the remaining 36 patients. Three novel LAMP2 frameshift mutations were found. They were c.808\_809 insG in exon 6, c.320\_321 insCATC in exon 3, and c.257_258delCC in exon 3, leading to a premature stop codon on cDNA analysis. The prevalence of Danon disease was seen in 6% (3 of 50) of unselected concentric LVH patients who underwent EMB, or 8% (3 of 36) after excluding cardiac amyloidosis through EMB. All the three patients were male teenagers with a mean age of 15 ± 1 years, and had mild mental retardation, two of the three with Wolff–Parkinson–White (WPW) syndrome and markedly increased left ventricular voltage. All the three patients had increased serum hepatic enzymes and creatine kinase (CK) concentrations. There was no death or cardiovascular hospitalization during 20 ± 15 months of follow-up. Conclusions Danon disease may account for a number of patients with concentric LVH who underwent EMB. Danon disease should be suspected in the male teenager with concentric LVH, especially with elevated serum hepatic enzymes and CK concentrations, and/or WPW syndrome with markedly increased voltage of the left ventricle. Genetic analysis of LAMP2 can help make the diagnosis.

Although endomyocardial biopsy (EMB) plays a crucial role in the final diagnosis in patients with heart failure of unknown etiology, the invasive nature of this technique limits its clinical application in China. The purpose of this study was to evaluate the clinical application of EMB in diagnosing cardiomyopathy with unexplained etiologies in China.Fifty-three consecutive patients (38 males, age 14 - 67 years, median 43 years) were included in the study who were initially diagnosed as unexplained cardiomyopathy and under EMB biopsy in Peking Union Medical College Hospital from 2006 to 2009. The patients were clinically divided into four groups: dilated, hypertrophic, restrictive and unclassified cardiomyopathy. Biopsies were performed via right internal jugular vein with the use of the bioptome under fluoroscopic guidance. Three to five endomyocardial samples were taken from each patient for light microscopy examination and one sample for electron microscopy was taken if necessary. For each patient, an initial clinical diagnosis, an EMB diagnosis and a final diagnosis prior to discharge were established. All the data were compared and analyzed for the evaluation of clinical utility of EMB in China.In 26 patients initially diagnosed with restrictive cardiomyopathy (RCM), the etiology of the condition was finally diagnosed using EMB in 15; including 13 amyloidosis and two eosinophilic myocarditis. We employed EMB in 19 patients clinically diagnosed as dilated cardiomyopathy and detected viral myocarditis in one patient, cardiac involvement due to polymyositis in four and doxorubicin-induced cardiomyopathy in one. In five patients with severe left ventricle hypertrophy undergoing EMB, one patient was diagnosed as autophagic vacuolar cardiomyopathy and one as mitochondrial disease. In the remaining three patients with unclassified cardiomyopathy, EMB revealed infiltration of eosinophils as the cause of atrial ventricular block in one patient. Final diagnoses were made in 24 of the total 53 patients (45%) based on the combination of EMB and clinical data. Transient atrial ventricular block in a patient with prior complete left bundle branch block was the only complication occurred during the procedures.The clinical application of EMB is safe. The combination of EMB and clinical data produced a better understanding of the mechanisms behind the clinically diagnosed cardiomyopathy in China.

To evaluate the prevalence of fetal anomalies in recent 10 years and explore the effective methods of early diagnosis and treatment.The clinical and pathological data of 116 pregnant women who underwent induced abortion in the second trimester due to fetal anomalies 1998 - 2007 were analyzed retrospectively.The fetal anomaly rate in the period 2003 - 2997 was 8.7 per thousand, significantly higher than that in the period 1998 - 2002 (3.1 per thousand, P0.001). The diagnostic methods of fetal anomalies used during the period 2003 - 2007 did not show significant differences compared with those used during the period 1998 - 2002. The gestational week when the fetal anomalies were detected in 2002 - 2007 was 19.3 weeks, not significantly preceded compared with that during 1998 - 2002 (22.4 weeks, P0.05). The top 5 fetal anomalies with high incidence rates were Down' syndrome, anencephalus, lip/palate cleft, fatal cystic hygroma of the neck, and cardiac anomalies. There were 30 cases of advanced maternal age over 35 years, 60.0% of whose fetuses showed chromosome abnormality.The incidence of fetal anomalies increases in recent years. The risk of fetal anomalies is high in the pregnant women in elder age. Pregnancy in advanced maternal age show high risk to occur fetal anomaly. Better approaches to diagnose fetal anomaly earlier are still to be found.

Eukaryotic translation initiation factor 5A2 (EIF5A2) plays an important role in tumor progression and prognosis evaluation. However, little information is available about its potential role in gastric cancer. This study aimed to investigate the function of EIF5A2 in tumor progression and its potential mechanisms. EIF5A2 expression was measured in human gastric cancer cell lines, the immortalized gastric mucosal epithelial cell line (GES-1) and human gastric cancer tissues and knocked down by RNA interference or upregulated by EIF5A2 plasmid transfection. Cell proliferation, migration and invasion were assessed in vitro. The downstream targets of EIF5A2 were examined by western blotting. EIF5A2 and its potential target metastasis-associated protein 1 (MTA1) expression were examined in 160 pairs of human gastric cancer and adjacent non-tumor specimens using immunohistochemistry (IHC) staining, and its correlation with clinicopathological features and survival was investigated. Knockdown of EIF5A2 or MTA1 caused an apparent suppression of HGC27 cell proliferation, migration and invasion. After knockdown of EIF5A2 in HGC27 cells, E-cadherin levels were upregulated and vimentin, cyclin D1, cyclin D3, C-MYC and MTA1 levels were downregulated. Upregulation of EIF5A2 in MKN45 cells resulted in the converse. IHC results showed a positive correlation between EIF5A2 and MTA1 expression in gastric cancers (P

To investigate surgical treatment results and clinical pathological specifics in the treatment of non-functional islet cell tumor.To perform retrospective analysis of 78 cases of non-functional islet cell tumor treated at Peking Union Medical College Hospital from July 1968 through January 2005, and summarize clinical symptoms and signs, primary diagnosis before surgery, surgical treatment, pathologic specifics and immuno-histological analysis.Of 78 cases, 27 cases (34.6%) was found in physical examinations, the most common symptoms was upper abdominal pain and upper abdominal discomfort, 30.7% (24 cases) and 26.9% (21 cases) respectively; the most common sign being abdominal masses 35.9% (28 cases). B-us and CT are most commonly used forms of preoperative examination, with positive rates being 98.6% (71/72), 100% (53/53) respectively. Operative mortality was 1.28%, Radical surgery of malignant cases with 5 year survival rate 75% (9/12). Immuno-histological examinations showed that tumors with multi peptide linked hormones 78.6% (55/70), a larger number of positive examinations of neuron specific enolase and chromaffin, 91.4% (32/35) and 79.4% (27/34) respectively. Insulin, glucagon, pancreatic polypeptide, somatostatin, vasoactive intestinal peptide and gastrin positive rates are 64.6% (42/65), 47.5% (22/53), 45.8% (22/48), 37.5% (21/56), 23.9% (11/46) and 22.6% (7/31).Non-functional islet cell tumor lack specificity, Bus and CT are primary examination methods, immuno-histological analysis indicates various different hormones, but lacks the presence of related clinical symptoms. Surgery is an effective form of treatment in the treatment of non-functional islet cell tumor, even with distal metastasis, immediate surgical removal and treatment, extend prognosis.

BACKGROUND: Familial recurrent hydatidiform mole is an extremely rare autosomal recessive condition in which affected individuals have a predisposition to molar pregnancies that are diploid but biparental, rather than androgenetic, in origin. A gene for this condition has been previously mapped to a 1.1 Mb region of chromosome 19q13.4. However, investigation of further families is needed to refine the location of the specific gene(s) involved. METHODS: We have recently identified two novel Chinese families in which four affected women had recurrent pregnancy loss including 14 complete hydatidiform moles (CHM). Fluorescent microsatellite genotyping was used to determine the origin of CHM in both families. Using a panel of polymorphic microsatellite markers, genotyping and haplotype analysis of the 19q13.4 chromosomal region was performed in both families. RESULTS: Genotyping of CHM from affected individuals confirmed their biparental origin and diagnosis of familial recurrent hydatidiform mole in both families. However, no significant homozygosity for the 19q13.4 candidate region was found in affected members of either family. CONCLUSION: Genotyping and haplotype analysis has shown that a mutation in 19q13.4 is unlikely to be responsible for recurrent CHM in the two Chinese families investigated and provides further evidence to support the hypothesis that, although extremely rare, this condition shows genetic heterogeneity.

Ting Gui,1,* Huimin Bai,1,* Jianfang Zeng,1 Zhaoji Zhong,1 Dongyan Cao,1 Quancai Cui,2 Jie Chen,2 Jiaxin Yang,1 Keng Shen11Department of Obstetrics and Gynecology, 2Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China *These authors contributed equally to this work Purpose: To investigate tumor heterogeneity in the recurrence of epithelial ovarian cancer demonstrated by polycomb group (PcG) proteins. Methods: Tissue microarrays containing matched primary and recurrent ovarian tumors from the same patients were constructed for detection of PcG protein expression. Survival analyses of clinicopathological parameters and expression of PcG proteins were performed on progression-free survival (PFS) and overall survival (OS) of patients. Genetic and epigenetic heterogeneity was explored in aspects of gene copy number and microRNA (miRNA) profiling. Results: PcG proteins were heterogeneously expressed in primary versus recurrent tumors (P

OBJECTIVE: It is widely recognized that the diagnosis of parathyroid carcinoma (PC) is often difficult because of the overlap of characteristics between malignant and benign parathyroid tumors, especially at an early stage. Based on the identification of tumor suppressor gene HRPT2/CDC73 and its association with hereditary and sporadic PC, screening of gene mutations and detection of parafibromin immunoreactivity have been suggested as diagnostic instruments of PC in Whites. There is little information about HRPT2/CDC73 mutations and its corresponding protein expression in patients with sporadic PC in Chinese population, and the long-term follow-up data is scarce. METHODS: Paraffin-embedded tissues were obtained from 13 patients with PC, 13 patients with parathyroid adenoma (PA) and 7 patients with parathyroid hyperplasia(PH), and 6 normal parathyroid (NP) tissues as controls. Peripheral blood from 11 patients with PC was collected. PCR products using Genomic DNA extracted from tumor tissues or blood as template was sequenced for HRPT2/CDC73 gene. Expression of parafibromin in tumor tissues was evaluated by immunohistochemical analysis. RESULTS: Six mutations in 6 of 13 patients with PC were identified, with three being novel. Four of them were germ-line mutations. Patients with mutations were susceptible to recurrence of the PC. Complete (8/13, 61.5%) or partial (5/13, 38.5%) loss of parafibromin expression was observed in PC tissues. All of tissue samples from normal parathyroid or benign parathyroid tumors displayed positive immunostaining of parafibromin except one adenoma. CONCLUSIONS: The present study supplies information on the mutations and protein expression of HRPT2/CDC73 gene and phenotypes of parathyroid carcinoma in Chinese population. And the expanded mutation database of this gene may benefit patients in the diagnosis and treatment of this disease.