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.

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.

OBJECTIVETo study the expression of EpCAM and E-cadherin in papillary thyroid carcinoma and to analyze its correlation with various clinicopathologic parameters.

METHODSImmunohistochemical 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.

RESULTSIn 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).

CONCLUSIONSE-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.

Antigens, Neoplasm ; metabolism ; Cadherins ; metabolism ; Carcinoma, Papillary ; metabolism ; secondary ; Cell Adhesion Molecules ; metabolism ; Cell Membrane ; metabolism ; Cytoplasm ; metabolism ; Epithelial Cell Adhesion Molecule ; Humans ; Lymphatic Metastasis ; Neoplasm Proteins ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology

OBJECTIVETo 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.

METHODSSixty-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.

RESULTSTwenty-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).

CONCLUSIONSBreast 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.

Beijing ; Carcinoma, Ductal, Breast ; diagnosis ; metabolism ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; RNA, Messenger ; metabolism ; Receptor, ErbB-2 ; metabolism

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.

Objective To investigate in situ mRNA expression of HER 2 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 HER 2 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 HER 2 gene amplification or protein overexpression , and has potential clinical utility.

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.

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.

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.

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.