NLRP7 and KHDC3L variants in Chinese patients with recurrent hydatidiform moles.

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.

Integrin Imaging with 99mTc-3PRGD2 SPECT/CT Shows High Specificity in the Diagnosis of Lymph Node Metastasis from Non-Small Cell Lung Cancer.

Purpose To evaluate an integrin imaging approach based on single photon emission computed tomography (SPECT)/computed tomography (CT) by using technetium 99m (99mTc)-dimeric cyclic arginine-glycine-aspartic acid (RGD) peptides with three polyethylene glycol spacers (3PRGD2) as the tracer to target the integrin αvß3 expression in lung cancer and lymph node metastasis. Materials and Methods With ethics committee approval and written informed consent, 65 patients (41 male, 24 female; mean age, 60 years ± 11 [standard deviation]) with suspicious lung lesions were recruited with informed consent. The patients underwent both 99mTc-3PRGD2 SPECT/CT and fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT within 1 week. Finally, 65 lung lesions in 53 patients were pathologically diagnosed as non-small cell lung cancer (NSCLC) and 14 lung lesions in 12 patients were benign. Per-region analysis of lymph nodes included 248 regions with metastasis and 56 negative regions. Twenty specimens from the removed lung lesions or lymph nodes were stained with integrin αvß3, CD34, and Ki-67 to correlate with the image findings. Receiver operating characteristic curve, z statistics, McNemar test, and χ2 analysis were used to compare the diagnostic performance of the two imaging methods. Results 99mTc-3PRGD2 SPECT/CT was found to be more specific than 18F-FDG PET/CT in the per-region diagnosis of lymph node metastasis (specificity, 94.6% vs 75.0%; P = .008) when the sensitivity of the two methods was comparable (88.3% vs 90.7%; P = .557). There was no significant difference between the two methods in the per-lesion diagnosis of lung tumor (z = 0.82, P = .410). The accumulation level of 99mTc-3PRGD2 was found in positive correlation with the integrin αvß3 expression (r = 0.84, P = .001) and microvessel density (r = 0.63, P = .011) in the tumors. Conclusion 99mTc-3PRGD2 SPECT/CT shows high specificity in the diagnosis of lymph node metastasis from NSCLC, which may benefit surgical decision making for the patients. © RSNA, 2016.

Expression of the potential cancer stem cell markers CD133 and CD44 in medullary thyroid carcinoma: A ten-year follow-up and prognostic analysis.

BACKGROUND AND OBJECTIVES: To investigate the expression profiles of cancer stem cells (CSCs) markers CD133 and CD44 in a cohort of medullary thyroid carcinoma (MTC) patients, and their prognostic values during 10-year follow-up. METHODS: MTC samples were obtained for H&E and immunohistochemical analysis. Survival analysis was performed using Kaplan-Meier method and log-rank test. RESULTS: Both the CD133 and CD44 positives were higher in MTC than control. High expression of CD133 and CD44 was positively correlated with capsule invasion and each other, and their co-expression was significantly correlated with capsule invasion, tissue invasion, and metastases at surgery. Tumor size, capsular invasion, tissue invasion, metastases at surgery, surgical plan, lymph node metastases, TNM stage, CD133, and CD44 were prognostic factors for overall survival (OS) and/or disease free survival (DFS). Both the CD133 and CD44 were unfavorable prognostic predictors for OS (P = 0.046, P = 0.03), while only CD44 was a significant predictor for DFS (P = 0.017). OS rate in CD133/CD44 co-expression group was significantly lower than that in non-co-expression group (χ(2) = 8.44, P = 0.004). CONCLUSION: Our study suggested the high expression of CD133 and CD44 in the MTC, and CD133 and CD44 expressions were correlated with capsule invasion and with OS. CD133 and/or CD44 may be prognostic factors for OS and/or DFS in our MTC patients.

[Expression of EpCAM and E-cadherin in papillary thyroid carcinoma and its clinicopathologic significance].

OBJECTIVE: To study the expression of EpCAM and E-cadherin in papillary thyroid carcinoma and to analyze its correlation with various clinicopathologic parameters. METHODS: Immunohistochemical study for EpCAM and E-cadherin was carried out in 91 cases of papillary thyroid carcinoma. Twenty-four cases of papillary hyperplasia of thyroid were used as controls. RESULTS: In all of the 24 cases of papillary hyperplasia, EpCAM was located on the cell membrane, while in the 91 cases of papillary thyroid carcinoma studied, EpCAM was located within the cytoplasm, with 36.3% (33/91) showing nuclear localization as well. In all the papillary hyperplasia cases studied, E-cadherin showed membranous expression. E-cadherin expression was reduced in 84.6% (77/91) of papillary thyroid carcinoma, as compared with the surrounding native thyroid parenchyma. Amongst the 33 cases of papillary thyroid carcinoma which showed nuclear localization of EpCAM, 30 cases also showed reduced E-cadherin expression. There was a positive correlation between nuclear expression of EpCAM and loss of E-cadherin expression (P = 0.000; Spearman correlation coefficient = 0.857). Nuclear expression of EpCAM correlated with follicular variant of papillary thyroid carcinoma and presence of extrathyroidal extension ( P = 0.037 and 0.033, respectively). Loss of E-cadherin expression correlated with age of patients and presence of lymph node metastasis (P = 0.018 and 0.010, respectively). CONCLUSIONS: E-cadherin expression is reduced in papillary thyroid carcinoma, as compared with native thyroid parenchyma and papillary hyperplasia. Papillary thyroid carcinoma shows loss of EpCAM membranous expression and increased cytoplasmic/nuclear accumulation. Detection of these two markers may provide a valuable reference in defining the biologic behaviors of papillary thyroid carcinoma, including extrathyroidal extension and lymph node metastasis.

[HER2 mRNA expression in breast cancers with equivocal immunohistochemical results using in situ mRNA hybridization].

OBJECTIVE: To investigate in situ mRNA expression of HER2 oncogene in breast cancers with equivocal immunohistochemical results, and to explore the potential feasibility of RNAscope technique in evaluating HER2 status in breast cancers. METHODS: Sixty-nine FFPE samples of invasive ductal breast cancer with equivocal HER2 immunohistochemistry results (IHC 2+) were collected from surgical excisions from Peking Union Medical College Hospital between June 2010 and June 2013. HER2 status and in situ mRNA expression were tested by fluorescence in situ hybridization (FISH) and RNAscope respectively using tissue microarray constructed from tumor paraffin blocks. The results of HER2 mRNA expression were scored 0 to 4 (from low to high levels) according to mRNA expression in 100 cancer cells. HER2 mRNA expression was evaluated in two groups of patients, with positive and negative FISH results. RESULTS: Twenty-three of the 69 samples were FISH positive, including 16 samples that were scored 4 by RNAscope (70%, 16/23), 6 samples were scored 3 (26%, 6/23) and one sample was scored 2 (4%, 1/23). High in situ mRNA expression (score 4 or 3) were observed in 96% of HER2 FISH positive samples. All of samples that were scored 4 by RNAscope were FISH positive. Forty-six samples were FISH negative, including 17 samples that were scored 3 by RNAscope (37%, 17/46), 25 samples were scored 2 (54%, 25/46), and 4 samples were scored 1 (9%, 4/46). CONCLUSIONS: Breast cancer with HER2 IHC 2+ could be further classified according to in situ mRNA expression status. Among them, RNAscope score of 4 could be one of the interpretation criteria for re-testing IHC 2+ samples. In situ detection of HER2 mRNA may be an additional candidate method of confirmation for HER2 gene amplification or protein overexpression, and has potential clinical utility.

Early biochemical response to ursodeoxycholic acid and long-term prognosis of primary biliary cirrhosis: results of a 14-year cohort study.

UNLABELLED: 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.

Ovary and uterus-sparing procedures for low-grade endometrial stromal sarcoma: a retrospective study of 153 cases.

OBJECTIVE: To discuss the optimal treatment options for low grade endometrial stromal sarcoma (LG-ESS). METHODS: Medical records of consecutive patients with LG-ESS in our institute were collected. The pertinent data, including clinicopathological characteristics, treatment and prognostic information were evaluated. RESULTS: A total of 153 cases of LG-ESS were included. The 5-year relapse free survival (RFS), overall survival (OS) and survival after relapse (SAR) rates were 66.1%, 95.8% and 82.9%, respectively. Ovary-sparing procedures, positive resection-margins, and myomectomy were the independent adverse factors for relapse (P<0.0001, =0.0041, and =0.0075, respectively). Post-menopause, cervical involvement, and positive lymphovascular space involvement were significantly associated with survival (P<0.0001, =0.0020, and =0.0163, respectively). Distance recurrence and macroscopically residual tumors negatively affected SAR (P=0.0137 and =0.0004, respectively). No benefit was found for lymphadenectomy in terms of both RFS and OS (P=0.1187 and =0.5138, respectively). Initial ovary-sparing procedures and myomectomy had no impact on OS (P=0.0810 and =0.8845, respectively). Adjuvant treatment had a slightly beneficial effect both on OS and SAR. CONCLUSION: Hysterectomy with bilateral salpingo-oophorectomy and complete resection of the macroscopic lesion should be treated as the initial and salvage mainstay treatments for LG-ESS patients. Ovary-sparing procedures could be considered for young women without cervical involvement; however, long-term follow-up should be mandatory. Myomectomy should only be conserved for young patients with a strong desire for future fertility, with fully informed consent; hysterectomy was recommended after the completion of pregnancy and delivery. However, the roles of lymphadenectomy and adjuvant treatment deserve further investigation.

Molecular portraits of heterogeneity related to cancer stem cells in human ovarian cancer.

PURPOSE: The aim of this study was to investigate molecular portraits of heterogeneity related to cancer stem cells (CSCs) in human ovarian cancer and to access the value in diagnosis and treatment. METHODS: Sixty specimens were collected in both cytoreductive and re-cytoreductive surgeries of 20 serous papillary ovarian adenocarcinoma cases. Expression density and distribution of 3 CSC markers (CD44, CD133, and CD117) and 3 stemness proteins (Bmi1, Nestin, and Oct3/4) were analyzed by immunohistochemical staining. Pairwise comparisons were performed among their expression in primary, metastasis, and relapsing tumors. RESULTS: Some molecules presented different localization in 1 tissue, like CD133 and CD117, and all but Oct3/4 expressed differentially in different specimens of 1 case. Compared to primary or metastatic cancers, recurrent cancers show higher expression of CD133, CD117, and Bmi1, as well as higher histological grades. CONCLUSIONS: Our study indicated that there exist extratumoral and intratumoral heterogeneity in ovarian epithelial cancers related to CSCs. And this is worth further studying.

The role of magnetic resonance imaging in pretreatment evaluation of early-stage cervical cancer.

OBJECTIVE: The aim of this study is to evaluate the accuracy of magnetic resonance imaging (MRI) in the preoperative assessments of primary tumor size, parametrial invasion, and pelvic lymph node metastasis in patients with early-stage cervical cancer. MATERIALS AND METHODS: A cohort of 125 patients with International Federation of Gynecology and Obstetrics stage IA2 to IIA cervical cancer who had preoperative MRI and underwent radical hysterectomy were enrolled and analyzed. The accuracy of preoperative MRI scan and pelvic examination in the measurement of tumor size was assessed based on postoperative measurement and pathologic findings. The accuracy of detection of lymph node status and parametrial invasion was also assessed by comparing the MRI and pathologic findings. RESULTS: The mean diameter of the tumor size measured by postoperative measurement, MRI, and pelvic examination was 2.97 ± 1.39 cm, 2.78 ± 1.24 cm, and 1.97 ± 1.70 cm, respectively. There were significant differences in the mean diameter of the tumor size between pelvic examinations and MRI scan or postoperative measurement (P < 0.0001). Based on postoperative measurement findings, accuracy of tumor size measurement between pelvic examination and MRI was determined by the degree of agreement with a difference of less than 0.5 or 1.0 cm. Pelvic examination and MRI had an accuracy of 24.75% and 39.60%, respectively, with a difference of less than 0.5 cm, and had an accuracy of 43.56% and 61.39%, respectively, with a difference of less than 1.0 cm. Correlation with postoperative measurement in tumor size was higher for MRI (r[s] = 0.481) than that for pelvic examination (r[s] = 0.362). The sensitivity, specificity, and accuracy of MRI in detecting lymph node metastasis were 27.78%, 85.98%, 77.60%, respectively. The negative predictive value of MRI in detecting parametrial invasion is 100%. CONCLUSIONS: Magnetic resonance imaging is an accurate noninvasive modality for preoperative evaluation of tumor size and also gives important information to parametrial invasion and lymph node status in patients with early-stage cervical cancer.

Clinical analysis of primary primitive neuroectodermal tumors in the female genital tract.

OBJECTIVE: The aim of the study was to investigate the clinical manifestations, diagnosis, treatment, and prognosis of primitive neuroectodermal tumors (PNETs) in the female genital tract. METHODS: From April 2001 to May 2013, the clinicopathologic characteristics, treatments, outcomes, and prognosis of 11 patients with PNET in the female genital tract were analyzed retrospectively at our hospital. RESULTS: The location of PNET in the 11 patients presented here included vulva (2 patients), cervix (2 patients), uterus and its ligament (5 patients), and the ovaries (2 patients). Ages ranged from 18 to 59 years (median, 31 years).The main clinical manifestations of PNET in the female genital tract are irregular vaginal bleeding (6 patients), pelvic mass, uterine enlargement, and rapidly increasing vulvar mass (8 patients), and vulvar pain and lower abdominal pain (5 patients). The CA125 levels of 8 patients were elevated before the operations and reduced to normal when the diseases were controlled, while the levels increased as the tumor was progressive. Results for the most commonly used immunohistochemistry studies revealed CD99 in 11 of the 11 tumors, synaptophysin in 6 of the 7 positive tumors, and neuron-specific enolase in 6 of the 6 tumors. Ten patients underwent surgical resection. Nine of them underwent preoperative or/and postoperative combination chemotherapy. The follow-up of 10 patients were available and ranged from 1 to 145 months (median, 30.5 months), 3 of whom experiencing recurrence. CONCLUSIONS: Primitive neuroectodermal tumor is very rare and can originate from any part of the female genital tract. The tumors had different manifestations but the same pathologic features. CA125 may be an important marker for prognosis and follow-up of PNET of the female internal genital tract.

N-wasp in pancreatic ductal adenocarcinoma: associations with perineural invasion and poor prognosis.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has long been acknowledged to have a dismal prognosis. Therefore, prognostic markers, especially molecular ones, are of interest. So far, expression of Neural Wiskott-Aldrich syndrome protein (N-WASP) and its associations with clinicopathologic variables and prognosis for patients with PDAC remain unknown. METHODS: N-WASP expression was detected by immunohistochemical staining in a tissue microarray consisted of tumor and nontumor samples from 86 patients with PDAC. The correlations of N-WASP expression with clinicopathologic features and overall survival were evaluated. In addition, risk factors of perineural invasion (PNI) were identified. RESULTS: High expression of N-WASP was more frequent in tumor than in nontumor tissues of PDAC patients (45.3 vs. 19.8%, p < 0.001). The rank of N-WASP grading was significantly higher in tumor tissues than in nontumor tissues (p = 0.048). Also, high expression of N-WASP in tumor tissues was significantly associated with PNI, and lymph node status had a marginally significant relation to tumoral N-WASP expression. Univariate analyses showed that, in addition to conventional clinicopathologic variables, including sex, histologic grade, PNI and lymph node metastasis, high tumoral N-WASP expression was an independent marker of PNI and served as a significant predictor of poor overall survival. The prognostic implication of N-WASP expression was not proven In the multivariate analysis. CONCLUSIONS: Our data showed highly up-regulated expression of N-WASP in PDAC tissues, its correlations with PNI, and its association with an unfavorable prognosis.

Clear cell carcinoma arising from abdominal wall endometriosis: a unique case with bladder and lymph node metastasis.

The malignant transformation of abdominal wall endometriosis is a rare event and poorly understood. Less than 30 cases have been reported in the literature. Most of the reported cases have a solitary tumor in the abdominal scar. A few cases have metastasis. Here we report a case of clear cell carcinoma in abdominal wall endometriosis with bladder and lymph system metastasis. The patient had a history of abdominal wall endometriosis and recently developed symptoms of urgent urination and inguinal mass. Physical examination and a computed tomography (CT) scan detected lymph node metastasis. CT and cystoscopy confirmed bladder involvement. The patient underwent extensive surgery and chemotherapy. Pathological analysis made a diagnosis of clear cell carcinoma with bladder and lymph node metastasis. The patient was followed up and died of the disease. Symptoms of bladder invasion and lymph node spread could be a sign of malignant transformation. Local invasion and lymph node spread are two important forms of tumor metastasis. Extensive lymph nodes metastasis might be related with poor prognosis.

Prognostic significance of epidermal growth factor-like domain 7 in pancreatic cancer.

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.

[Research advances in epithelial-mesenchymal transition in thyroid carcinoma].

Increasing evidences have demonstrated the roles of epithelial-mesenchymal transition in tumor invasion and metastasis. In the invasive front of papillary thyroid carcinoma, the expressions of adhesion molecules are often lost. In anaplastic thyroid carcinoma, tumor cells showing cancer stem cell characteristics have been identified. Epithelial-mesenchymal transition may thus play a key role in the progression of thyroid cancer. Therefore, it provide new insight for the development of targeted drugs for anaplastic thyroid carcinoma.

Low expression of PAI-2 as a novel marker of portal vein tumor thrombosis and poor prognosis in hepatocellular carcinoma.

BACKGROUND: Plasminogen activator inhibitor (PAI)-2 was previously shown to be less frequently expressed in hepatocellular carcinoma (HCC). The present study was designed to investigate the clinical, pathological, and prognostic significance of PAI-2 expression in HCC. METHODS: Expression of PAI-2 was detected immunohistochemically for specimens from 78 patients with HCC after hepatic resection and correlated with clinicopathological features and patient survival. Risk factors of portal vein tumor thrombosis (PVTT) were also analyzed. RESULTS: Positive PAI-2 staining was observed in tumor and non-tumor tissues from 21 (26.9%) and 56 (71.8%) patients, respectively. Plasminogen activator inhibitor-2 negativity in tumor tissues was significantly associated with PVTT, with a high sensitivity not only in univariate analysis but also in multivariate analysis. In addition, positive PAI-2 staining was related to smaller tumor size and prolonged patient survival. The Cox regression model identified intratumoral PAI-2 staining as an independent prognosticator in patients with HCC after resection. CONCLUSIONS: Our data demonstrated that low expression of PAI-2 serves as a novel marker of PVTT and poor prognosis in HCC.

Notch1 contributes to chemoresistance to gemcitabine and serves as an unfavorable prognostic indicator in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) carries frequent chemoresistance and extremely dismal prognosis. The underlying mechanisms remain to be further elucidated. We here report the role of Notch1 in gemcitabine resistance and its prognostic significance in PC. METHODS: A small interfering RNA (siRNA) specifically targeting Notch1 was transiently transfected into three PC cell lines (AsPC-1, BxPC-3, and MIA PaCa-2), followed by examination of chemosensitivity to gemcitabine. On the other hand, Notch1 expression was evaluated immunohistochemically and correlated with clinicopathological and prognostic variables. RESULTS: Successful knockdown of Notch1 by specific siRNA induced increased chemosensitivity to gemcitabine in all three cell lines. Immunohistochemical staining revealed that Notch1 was highly expressed in PC tissues (54.8 %), in contrast to that in para-tumor tissues (16.4 %). In addition, Notch1 positivity was significantly correlated with early-term metastasis and shortened overall survival. Multivariate Cox regression identified Notch1 as an independent prognostic factor. CONCLUSIONS: Notch1 contributes to chemoresistance to gemcitabine, and serves as a significant indicator of unfavorable prognosis in PC.

The findings of electrocardiography in patients with cardiac amyloidosis.

OBJECTIVE: The electrocardiography (ECG) was the simplest and common adjunctive diagnostic tool for cardiac amyloidosis (CA). We sought to clarify the findings of ECG in patients with CA in order to early identification of CA according to the findings of ECG. METHODS: A total of 276 patients with diagnosis of systemic amyloidosis admitted to Peking Union Medical College Hospital from January 2000 to December 2011, were enrolled. Two groups were classified according to the cardiac involvement or not, namely CA (n = 189) and control (n = 87) groups. The low voltage on limb leads defined by the amplitude of the QRS complex in each limb leads ≤0.5 mV. The pseudo-infarct pattern defined by the presence of pathologic Q waves on at least two contiguous leads on ECG without obstructive coronary artery disease. RESULTS: The mean age was 55 ± 12 (15-88) years, 168 patients (61%) were male. Atrial arrhythmia (15.9% vs 3.4%, P = 0.003), low voltage on limb leads (54.5% vs 20.7%, P < 0.001), atrioventricular block (14.8% vs 1.1%, P = 0.001) and pseudo-infarct pattern (40.2% vs 4.6%, P < 0.001) were more prevalent in CA than control groups. The combination of low voltage on limb leads and pseudo-infarct pattern was more common (28.0% vs 2.3%, P < 0.001) in CA than control groups. The sensitivity, specificity, positive and negative predictive values of the presence of low voltage on limb leads and pseudo-infarct pattern for the diagnosis of CA were 28%, 98%, 96%, and 39%, respectively. CONCLUSION: In CA patients, low voltage on limb leads and pseudo-infarct pattern were the most common ECG findings. Atrial arrhythmia and atrioventricular block were the most common arrhythmias in CA patients. The combination of low voltage on limb leads and pseudo-infarct pattern had high specificity and positive predictive value for the diagnosis of CA.

Danon disease as a cause of concentric left ventricular hypertrophy in patients who underwent endomyocardial biopsy.

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.

[Value of detecting epidermal growth factor receptor mutations in non-small cell lung cancer tissue by TaqMan-amplification refractory mutation system].

OBJECTIVE: To explore the value of detecting mutations on epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) tissue by TaqMan-amplification refractory mutation system (TaqMan-ARMS). METHODS: TaqMan-ARMS and DNA sequencing were used to detect the EGFR exon 19 and 21 mutations in tumor tissues and the samples collected from 199 patients at 4 different 3A hospitals in Beijing from January 2008 to March 2011. RESULTS: The rate of mutations in EGFR exon 19 and 21 was 19.1% (38/199), according to their different pathological types. Based upon TaqMan-ARMS, the classification was as followed: adenocarcinoma (35.0% (36/103)), squamous carcinoma (2.2% (2/93)) and adenosquamous carcinoma (0). According to DNA sequencing, they were 19.6% (39/199), 35.9% (37/103), 2.2% (2/93) and 0 respectively. Thus, no statistically significant difference existed between two methods (McNemar Test, P = 1.000, κ = 0.984). The mutation rate of adenocarcinoma was higher than those of squamous and adenosquamous carcinoma. CONCLUSION: The detection of EGFR mutations is highly consistent in the NSCLC tissue by the methods of TaqMan-ARMS and DNA sequencing.

[Clinicopathologic characteristics of primary thyroid-like follicular carcinoma in kidney].

OBJECTIVE: To explore the clinicopathological characteristics of primary thyroid-like follicular carcinoma of the kidney. METHODS: A case of primary thyroid-like follicular carcinoma of the kidney was studied with histology and immunohistochemical staining, and its clinical and pathological findings were further analyzed with review of the literature. RESULTS: The patient was a 26-year-old asymptomatic woman who had a kidney mass during her annual physical examination. The tumor was well-circumscribed. Pathologically, the tumor showed follicular structures with colloid-like material in the lumina. Immunohistochemically, the tumor cells showed intense staining for CK7 and vimentin and negative for thyoid transcripation factor-1, thyroglobulin, thyoid peroxidase and RCC. CONCLUSIONS: The diagnosis of primary thyroid-like follicular carcinoma of the kidney is based on the characteristic follicular architecture with colloid-like material, and the metastasis from a thyroid follicular carcinoma must be excluded clinically and pathologically before making the final diagnosis.