HER2 gene status and mRNA expression in immunohistochemistry 1+ breast cancer / 中华病理学杂志

Objective@#To investigate human epidermal growth factor 2 (HER2) gene status and in situ mRNA expression in breast cancers with immunohistochemistry(IHC) 1+ , and to reveal HER2 positive rate in these patients to provide reference data for obtaining precise HER2 results and modifying relevant clinical strategy to breast cancer.@*Methods@#Sixty-five IHC 1+ formalin-fixed and paraffin-embedded samples of invasive breast carcinoma of no special type (IBC-NST) were collected by surgical operation at Peking Union Medical College Hospital during 2011 to 2013. HER2 status and in situ mRNA expression were tested by fluorescence in situ hybridization (FISH) and RNAscope, respectively, by using tissue microarray. Metastatic lymph node was re-tested by FISH if HER2 status was equivocal or negative and with high expression of mRNA in the primary lesion.@*Results@#Four of 65 samples (6.2%) were FISH positive, which included 2 cases of HER2/CEP17>2 and average HER2 copy number>4 and 2 cases of HER2/CEP17<2 and average HER2 copy number>6. In the 4 samples of HER2 positive, 2 patients showed high in situ mRNA expression (3 scores by RNAscope), 2 patients showed moderate in situ mRNA expression (2 scores by RNAscope). In addition, 3 specimens with HER2/CEP17>2 and average HER2 copy number<4 were found in all patients, which included 2 cases of high in situ mRNA expression (3 and 4 scores by RNAscope) and 1 cases of moderate in situ mRNA expression (2 scores by RNAscope). There was no significant association between HER2 status or mRNA expression and clinicopathological characteristics, including tumor size, histopathological differentiation, lymph node metastasis and lymphovascular invasion (P>0.05).@*Conclusions@#A small number of HER2 IHC 1+ patients exist mRNA expression by using FISH method, which suggested that these patients might benefit from anti-HER2 therapy potentially. Since the importance for patients with breast cancers to develop diagnostic and therapeutic strategies from accurate molecular typing, further studies based on a larger cohort are needed to validate our findings.

Clinical and brain histopathology study in nine patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective To investigate the post-mortem brain histopathology in patients with systemic lupus erythematosus (SLE).Methods The medical records and cerebral autopsy tissue of nine patients with SLE autopsied during 1956--2000 in Peking Union Medical College Hospital were collected and reviewed.Results Nine patients were all female and the average age was (29±11) years.Eight out of nine patients clinically presented with neurological manifestations.Brain histopathology changes were identified as follow:brain parenchyma change was shown in eight cases (8/9),cerebral hernia in six cases (6/9),cerebral hemorrhage in four cases (4/9),infarction in three cases (3/9),ventricular dilation in three cases (3/9),meningitis in two cases (2/9) and vasculopathy in one case (1/9).Vasculitis was not shown in any patients.Conclusion The brain histopathology in SLE includes vasculopathy,infarction,hemorrhage,infection,meningitis,ventricular dilation,cerebral hernia,brain parenchyma change,etc.Among the above changes,brain parenchyma changes,cerebral hernia and hemorrhage are the most commonly shown,while vasculitis is uncommonly presented.SLE patients with brain histopathology changes may even without clinically manifestation.All patients with SLE should be alert to neurological involvement.

HER2 mRNA expression in breast cancers with equivocal immunohistochemical results using in situ mRNA hybridization / 中华病理学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Expression of EpCAM and E-cadherin in papillary thyroid carcinoma and its clinicopathologic significance / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of EpCAM and E-cadherin in papillary thyroid carcinoma and to analyze its correlation with various clinicopathologic parameters.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Treatment strategy for medullary thyroid cancer / 国际肿瘤学杂志

Medullary thyroid cancer is a kind of rare malignancy arising from unregulated replication of parafollicular C cells of the thyroid gland. Therapeutic approaches to patients with medullary thyroid cancer have their own features,which are different from those to patients with papillary thyroid cancer,the most com-mon type of thyroid cancer. The targeted therapy using tyrosine kinase inhibitors has brought new hope for the management of aggressive medullary thyroid cancer in recent years.

Negative transperineal template-guided saturation biopsy with serum PSA ≥30 μg/L: a report of 44 cases / 中华泌尿外科杂志

Objective To report outcomes of patients with PSA ≥ 30 μg/L with initial negative transperineal template-guided saturation biopsy (TTSB). Methods From 2003 to 2010,a total of 1824 patients underwent transperineal saturation biopsies with the prostate template at the Peking Union Medical College Hospital.44 of them had initial negative biopsy with PSA ≥ 30 μg/L were reviewed in this study.The mean age was 68 years old (range,51 to 80).The mean biopsy cores were 28.7 (range,11 to 44).The median PSA level was 40 μg/L (range,30 to 128),and the median prostate volume was 73 ml (range,30 to 190).They were divided into four groups:TURP group,chronic prostatitis group,repeat biopsy group and miscellaneous group. Results Patients were followed up for a mean of 49 months (range,12 to 91).All patients of TURP group (15 cases) were identified as prostatic hyperplasia by postoperative pathology.2 of them had a second TTSB for PSA ＞ 10 μg/L after TURP,which were negative.5 patients of chronic prostatitis group had a declining PSA level after antibiotic therapy for 3 to 4 weeks.One patient took a second biopsy,which was identified as prostatitis.All patients of repeat biopsy group (18 cases) showed no significant decrease in PSA level during follow-up and undertook biopsies 2 to 4 times,6 of which were proved to be prostate cancer.All patients of the miscellaneous group (6 cases) had a declining PSA and didn't take a second biopsy. Conclusions Close follow-up and regular PSA testing for patients who had a high PSA level with initial negative biopsy would be help to avoid both false negative of prostate cancer and unnecessary biopsy.

Study on pathological characteristics of eutopic endometrium in endometriosis / 中华妇产科杂志

Objective To study the pathologic characteristics of eutopic endometrium in patients with endometriosis.Methods Pathologic characteristics of eutopic endometrium were studied in 176 patients with endometriosis in Peking Union Medical College Hospital from January 2007 to December 2008 retrospectively.Results About 72.2％(127/176)of eutopic endometrium were in proliferative phase,19.9％(35/176)of were observed as endometrial polyp,including 32 cases with simple endometrial polyp and 3 cases with abnormal hyperplasia combined with endometrial polyp.And 4.0％(7/176)showed abnormal hyperplasia.The incidence of pathologic changes in eutopic endometrium was 22.2％(39/176).Among 53 endometriosis patients combined with infertility,the incidence of pathologic changes of eutopic endometrium was 35.9％(19/53),which was significantly higher than 16.3％ in non-infertile patients (x2 =8.24,P =0.004).Among 65 cases with irregular menstruation,the incidence of endometrial polypus and endometrial hyperplasia were 20.0％(13/65)and 10.8％(7/65),which were significantly higher than 17.1％(19/111)and 0 in normal menstruation patients(x2 =13.839,P =0.003).Conclusions The eutopic endometrium of endometriosis were in proliferative phase state.The pathologic changes of eutopic endometrium were more in patients combined with infertility and irregular menstruation.

Clinical and pathological features of primary biliary cirrhosis / 中华风湿病学杂志

Objective The aim of this study was to describe the clinical and pathological features of primary biliary cirrhosis(PBC) and their correlation.Methods Liver biopsy specimens were obtained through percutaneous needle puncture from twenty four patients with PBC who had not been diagnosed or treated before.These samples were fixed in formaldehyde and embedded in paraffin for routine histological examination.Pathologic stages based on Ludwig criteria,fibrosis,portal and periportal inflammation,lymphocytic periportal piecemeal necrosis,ductular proliferation,intralobular hepatocyte necrosis,the degree of ductopenia and relevant laboratory results were recorded.Statistics method used was x2 or t-test,Mann-whitmey U nonperametric test and Pearson's or Spearman's correlation analysis.Results The pathological stages,degree of fibrosis were positively correlated with total bilirubin (TBIL) level,total bile acid (TBA),cholesterol (CHO),IgG levels,and were negatively correlated with serum albumin(ALB) level(r=-0.527,P=0.030; r=-0.503,P=0.039) ,percentage of eosinophilic cells (EOS) ( r=-0.554,P=0.021; r=-0.502,P=0.040).Lymphocytic periportal piecemeal necrosis was positively correlated with alkaline phosp-hatase (ALP),TBIL,DBIL,TBA,and also tumor necrosis factor-αt (TNF-αα) levels(r=0.617,P=0.006).Conclusion TBIL,DBIL,TBA,CHO,IgG and ALB,EOS are good surrogate markers for disease sever ity and reversibility of PBC,while ALP,TNF-Cα,TBIL,DBlL,TBA can be used as markers for disease activity.

The clinico-pathological manifestation of cardiac involvement in eosinophilic diseases / 中华内科杂志

Objective To investigate the clinical and pathological features of eosinophilic diseases with cardiac involvement Methods We analyzed the clinical and cardiac pathological data of 7 patients with eosinophilic diseases with cardiac involvement under endomyocardial biopsy or autopsy.Results Seven patients (5 male, average age 51 years) were enrolled.Four patients were diagnosed as idiopathic hypereosinophilic syndrome and three were Churg-Strauss syndrome.Peripheral blood eosinophila count increased significantly in all patients.Cardiac involvement included angina pectoris, myocardial infarction, heart failure, presyncope and sudden death.Electrocardiogram showed cardiac ischemia, bundle branch block and third degree atrioventricular block.Echocardiography suggested ventricular and atrial enlargement, decreased ventricular systolic function, pulmonary hypertension, valvular prolapse and insufficiency and endocarditis.Pathology displayed infiltration of eosinophils, formation of granulomata, necrotizing vasculitis, myocardial necrosis and endomyocardial fibrosis in heart.Coronary artery could be also affected and led to myocardial infarction.Conclusions Cardiovascular complications of eocinophilic diseases are a major source of morbidity and mortality in these disorders.The manifestations are multiple and early recognition and treatment with steroid and immunosuppressant can improve prognosis.

Color Doppler flow imaging and CD34, VEGF immunohistochemical study of the solid thyroid nodules / 中华超声影像学杂志

Objective To evaluate angiogenesis of the benign and malignant solid thyroid nodules with color Doppler ultrasound and immunohistochemistry staining. Methods Fifty-six solid thyroid nodules in 55 patients (28 papillary thyroid cancer, 23 goiter, 4 adenoma, 1 Hashimoto' s disease) were observed before surgery with color Doppler ultrasound. Pathological specimens of paraffin-embedded were immunohistochemically stained with CD34 and VEGF antibody. Results There were significant differences between the benign and malignant thyroid nodules in vascular morphology and regional rich blood flow. The irregular or less irregular vessels were found in 75 % of the malignant nodules. Regional rich blood flow or suspicious regional rich blood flow were found in 64. 3% of malignant nodules. The regular vessels were found in 89. 3% of the benign nodules, non-regional rich blood flow was found in 71.4% of the benign nodules. The number of CD34 in malignant lesions [(37.31 ± 11.55)/HP] was significantly higher than benign lesions [(29. 02 ± 8.32)/HP, P = 0.04]. There was a significantly difference of VEGF expression between the benign and malignant nodules which was higher in malignant nodules than in benign nodules(P ＜ 0.01). Conclusions Compared with the benign nodules, the vessles in malignant thyroid nodules were irregular,the distribution of vessles was asymmetry and angiogenesis was active.

Genetic genesis of choriocarcinoma / 中华妇产科杂志

Objective To distinguish choriocarcinoma from gestational or non-gestational choriocarcinoma and also identify the causative pregnancy of gestational choriocarcinoma by the genetic origin through molecular genetic analysis. Methods Twelve patients with choriocarcinoma, who had experienced surgery prior to chemotherapy were enrolled in this study. All 12 cases were diagnosed pathologically as choriocarcinoma. Peripheral venous blood samples and formalin-fixed paraffin-embedded blocks of choriocarcinoma tissue microdissected from haematoxylin and eosin-stained sections of tissue by microdissection method were available from the patient and (or) her husband. DNA was then prepared from the couples' blood samples and choriocarcinoma tissue by using standard techniques. PCR amplification and fluorescent microsatellite genotyping were performed by using DNA from the couples and captured choriocarcinoma tissues. The genetic contributions to the choriocarcinoma tissue were determined by comparing the fragments of genes from the choriocarcinoma tissue to those from blood samples of the couples. Results The primary lesion was ovary in 7 cases, but only 4 of them had the maternal contribution, indicating a non-gestational origin; the other three were gestational choriocarcinoma. The primary lesion was uterus in 5 cases, which were all gestational choriocarcinoma confirmed by genetic analyses. The causative pregnancies of the 8 cases with gestational choriocarcinoma were identified as androgenetic complete hydatidiform mole (AnCHM) in six cases and normal pregnancies in two cases, respectively. Conclusion Microsatellite polymorphism analysis is a molecular approach for distinguishing the non-gestational choriocarcinoma from the gestational one, and also be used to identify the causative pregnancy of gestational choriocarcinoma.

The efficacy and safety of intravenous bisphosphonates in the treatment of primary hyperparathyroidism complicated by hyperculcemia crisis / 中华内科杂志

creatinine concentration. Conclusion Bisphosphonates can decrease serum total calcium levels in hypercalcemia crisis caused by PHPT effectivelywith mild adverse events.

Intravascular T-cell lymphoma:one case report and Hterature review / 白血病·淋巴瘤

Objective To improve the recognition of intravaseular lymphoma.Methods One case of intravaseular T-cell lymphoma was reported and the related literatures were reviewed.Results Intravaseulal T-cell lymphoma presenting with fever,rash and haemophagocytie syndrome is rare.Although the patient was given chemical therapy,he was died of liver failure and gastrointestinal bleeding.Conclusion Intravascular T-cell lymphoma is rare,often diagnosed after autopsy and shows a rapidly aggressive course.

Subcutaneous panniculitis-like T-cell lymphoma:a report of 6 cases / 基础医学与临床

Objective To investigate the clinical and pathological characteristics as well as immunophenotypes of subcutaneous panniculitis-like T-cell lymphoma for its differential diagnosis with other similar diseases.MethodsThe clinical、histological and immunophenotypic features of 6 cases were described in detail and related literatures were reviewed.Results All of 6 patients presented with subcutaneous nodules or /and erythematous plaques without lymph nodes swelling and with 5 cases had fever,one case developed to ulcer from its nodules.All of 6 patient presented typical histological changes and 2 of them associated with prominent hemophagocytic syndrome.The neoplastic cells were of T-cell phenotype.Two patients under went an aggressive clinical course with short survival period of 9～16 months and four patients who treated with chemotherapy have an improved survival state,but two of them had recurrence.Conclusion SPTCL is a uncommon type of T-cell lymphoma with clinical and pathological characteristics,and it needs to be differentiated from benign panniculitis or other lymphomas of the skin.

Trastuzumab decreases the proliferation of endothelium induced by TCM from MDA-MB-231 / 基础医学与临床

Objective To investigate the effect of trastuzumab,a special blocker of epidermal growth factor receptor-2(HER-2) on proliferation and apoptosis of human umbilical vein endothelial cells(HUVECs) exposed to tumor conditioned medium(TCM).Methods HUVECs were cultured and exposed to TCM and trastuzumab was used as an intervention approach.Their proliferation,apoptosis and cell cycle distribution were measured by MTT and flow cytometery(FCM).Intra-tumor microvessel density(MVD) and HER-2 expression were tested by immunohistochemistry(IHC).Results Following the stimulation of MDA-CM,HUVECs showed higher proliferating and anti-apoptotic ability(P

Fibrous histiocytoma of the laryngeal glottis / 中国耳鼻咽喉头颈外科

A case of a fibrous histiocytoma (FH) of the larynx in a 54-year-old male is reported. Laryngeal fibrous histiocytoma is uncommon. The case recurred several times over 4-year period. Its pathology is described including arguments on potential malignancy and the way of management.

Interactions between the epidermal growth factor receptor and typeⅠ protein kinase A in therapy of malignant tumor / 中国癌症杂志

The overexpression of EGFR and the typeⅠcAMPdependent protein kinase(PKAⅠ) has been found in most cancer tissue and tumour cells.The blockade of EGFR activation by using anti-EGFR monoclonal antibodies(MAbs) and inhibition of PKAⅠ expression by specific pharmacological agents such as the selective cAMP analogue 8-Cl-cAMP has been proposed as a potential anticancer therapy.We have shown that an interaction between EGFR and PKAⅠ occurs through direct binding of the RⅠsubunit to the Grb2 adaptor protein.We have demonstrated that the functional interaction between the EGFR and the PKAⅠ pathways could have potential therapeutic implications.In fact,the combined interference with both EGFR and PKAⅠ with specific pharmacological agents,has a cooperative antiproliferative effect on human cancer cell lines in vitro and in vivo.Studies on the antitumor activity of this combination are under human clinical trial evaluation.