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.

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.

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 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.

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.

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.

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.

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

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.

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.